Knowledge-map and bibliometric analysis of scientific research on FDA-approved Chimeric Antigen Receptor T cell products (2015-2024).

Introduction

Among the most ground-breaking and novel therapies introduced in recent years is autologous Chimeric Antigen Receptor T cells (CAR-T), which is a personalized adoptive cellular immunotherapy, where patient-derived T cells are genetically engineered to express synthetic receptors that recognize specific tumor antigen [ 1 ]. CAR-T constructs typically include an extracellular single chain variable fragment targeting tumor antigen (e.g. CD19), linked to intracellular CD3ζ and one or more co-stimulatory domains, enabling potent and sustained T cell activation and cytotoxicity [ 2 , 3 ]. This personalized approach ensures high specificity to cancer cells and reduces the risk of harmful issues [ 4 ]. This approach of using patient’s own T cells is called autologous CAR-T cells, which eliminates the risk of immune rejection and graft-versus-host disease. A second approach, called allogenic CAR-T cells, in which the T cells are derived from healthy donors, offers an “off-the-shelf” and rapid procedure compared with the autologous approach [ 5 – 8 ]. However, gene editing procedure may be required in allogenic CAR-T cells therapy to minimize immune reaction and rejection [ 9 , 10 ].

The U.S. Food and Drug Administration (FDA) has approved several CAR-T cell products in the past decade, including tisagenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel), brexucabtagene autoleucel (brexu-cel), lisocabtagene maraleucel (liso-cel), idecabtagene vicleucel (ide-cel), and ciltacabtagene autoleucel (cilta-cel) [ 11 ]. These advanced cellular therapies have significantly transformed clinical practice by introducing a new era of personalized, living drugs that can be engineered to selectively target malignant cells [ 12 ]. The introduction of CAR-T cell products has redefined treatment paradigms, especially in hematologic malignancies, by offering options where conventional therapies often fail [ 13 – 16 ]. The CAR-T cell therapy has undergone remarkable evolution since its inception, with successive generations designed to enhance its efficacy, persistence, and safety [ 17 – 21 ]. The first-generation CAR-T cells incorporated only the CD3ζ signaling domain, enabling cytotoxic activity, but showing limited persistence and suboptimal clinical outcomes due to the absence of co-stimulatory signals [ 22 ]. To address this, the second-generation CARs, which form the basis of most current FDA-approved therapies, introduced an additional co-stimulatory domain, such as CD28 and 4-1BB, greatly improving T cell expansion, survival, and anti-tumor potency. Building further, third-generation CARs integrated two co-stimulatory domains aiming to synergize T cell activation [ 16 ]. The fourth generation CARs, also known as TRUKS, incorporate inducible cytokines genes enabling CAR-T cells not only to kill but also to modulate tumor cell microenvironment [ 23 ]. The fifth generation CARs activate the JACK-STAT pathway upon antigen engagement improving efficacy and durability [ 22 ].

Given the novelty and recent introduction of FDA-approved CAR-T cell therapy, there is a compelling need to map the research landscape systemically. Bibliometric analysis, a quantitative method that uses statistical and network-based approaches to analyze academic literature, offers a powerful tool to evaluate publication trends, citation impact, prolific countries/authors/institutions, collaborative networks, and emerging hotspots in a specific research domain [ 24 ]. Unlike traditional narrative reviews, which are often subjective and selective, or systematic reviews, which focus narrowly on clinical outcomes or interventions using strict inclusion criteria, bibliometric analysis provides a broad, objective, and data-driven overview of the structure and dynamics of scientific research [ 25 , 26 ]. Bibliometric analysis is particularly useful in fast evolving fields such as immunotherapy, where the volume and diversity are rapidly expanding. The objective of the current study is to conduct a comprehensive knowledge-map and bibliometric analysis of FDA approved CAR-T cells. The study aims to identify leading authors, institutions, countries, journals; assess citation patterns and collaborative networks; and highlight the most influential articles and thematic trends. Although several bibliometric and knowledge-map studies have been published on CAR-T cells in recent years, there remains a significant gap in the literature that justifies the need for a focused bibliometric analysis specifically targeting FDA CAR-T cell products. Existing studies have predominantly explored the broader landscape of CAR-T cell research, encompassing basic science, preclinical studies, investigational therapies, and trials across various malignancies, including hematologic and solid tumors [ 27 – 34 ]. Therefore, the current study offers a novel, timely, and clinically relevant angle that sets apart from prior studies. Unlike previously published bibliometric studies that assessed CAR-T cell therapy as a broad field, the current study will focus exclusively on market-authorized, FDA approved therapies, which will generate focused and real-world research implementation of CAR-T cells.

Methods

BIBLIO checklist

The current study adheres to the preliminary guideline for reporting bibliometric reviews of biomedical literature (BIBLIO) [ 35 ].

Search strategy and data source

To systematically explore the scientific landscape of FDA approved CAR-T cells, a comprehensive bibliometric analysis was conducted using the Scopus database, chosen for its extensive coverage of peer-reviewed scientific literature and robust citation indexing. Relying exclusively on a single database to retrieve relevant data was justifiable given that Scopus is highly inclusive of both PubMed and Web of Science [ 36 – 38 ]. Secondly, the use of title-abstract search strategy made the use of a single database acceptable and methodologically sound and can retrieve all or most published documents, especially in emerging research topics such as CAR-T cell therapy. Thirdly, bibliometric analysis studies are different from systematic or scoping reviews where multiple databases are used to answer a specific question.

In the current study, the search was performed to identify relevant studies published between 2015 and 2024. The search strategy was carefully developed using keywords related to CAR-T cell products approved by the FDA. The following keywords were used: “tisagenlecleucel”, “Kymriah”, “axicabtagene ciloleucel”, “Yescarta”, “axi-cel”, “brexucabtagene autoleucel”, “Tecartus”, “brexu-cel”, “lisocabtagene maraleucel”, “Breyanzi”, “liso-cel”, “idecabtagene vicleucel”, “Abecma”, “ide-cel”, “ciltacabtagene autoleucel”, “Carvykti”, “cilta-cel”. The keywords include generic names, trade names, and abbreviated names of FDA approved CAR-T cells [ 36 ]. No language restriction was used and all types of documents, except errata and retracted, were included in the analysis. The full search query looked as this:

(TITLE-ABS (“Tisagenlecleucel” OR “Kymriah” OR “Axicabtagene ciloleucel” OR “Yescarta” OR “Axi-cel” OR “Brexucabtagene autoleucel” OR “Tecartus” OR “Brexu-cel” OR “Lisocabtagene maraleucel” OR “Breyanzi” OR “Liso-cel” OR “Idecabtagene vicleucel” OR “Abecma” OR “Ide-cel” OR “Ciltacabtagene autoleucel” OR “Carvykti” OR “Cilta-cel”)) AND ( LIMIT-TO ( SRCTYPE , “j”)) AND ( LIMIT-TO ( PUBSTAGE , “final”)) AND ( EXCLUDE ( DOCTYPE , “er” )) AND ( LIMIT-TO ( PUBYEAR , 2016 ) OR LIMIT-TO ( PUBYEAR , 2017 ) OR LIMIT-TO ( PUBYEAR , 2018 ) OR LIMIT-TO (PUBYEAR , 2019 ) OR LIMIT-TO ( PUBYEAR , 2020) OR LIMIT-TO ( PUBYEAR , 2021) OR LIMIT-TO ( PUBYEAR , 2022) OR LIMIT-TO ( PUBYEAR , 2023) OR LIMIT-TO ( PUBYEAR , 2024 ) OR EXCLUDE ( PUBYEAR , 2025)) .

Validation and quality check

The validity and precision of the search strategy employed in the current study was adopted from a previously published bibliometric study where the research output of the top 10 active authors obtained by the search query was compared with their actual research output obtained by manual counting of the documents published by each author in the field of interest using Google Scholar [ 39 ]. The numbers obtained by the search strategy and those obtained by manual investigation were tested for correlation. The results obtained showed a significant and strong correlation ( p = 0.001, Pearson correlation coefficient = 0.82), indicating a high validity of the search strategy. This validation step was endorsed by manual review of the top 100 cited documents to confirm their alignment with the research topic. The manual review was carried by two volunteering colleagues (A.A and W.S) in the field of biomedical sciences. The results of the manual review showed high consistency between the selected documents and the topic being investigated. Furthermore, since this field is recent and the names of the FDA approved CAR-T products are unique, the probability of false-positive results remain very low. At the same time, the use of title-abstract search methodology made the probability of false-negative results very low too.

Bibliometric indicators and visualization

The bibliographic data obtained from Scopus were exported and analyzed using both descriptive bibliometric indicators and network-based visualization tools. Key descriptive indicators included average annual growth rate (AAGR), top 10 prolific countries, and journals [ 40 ]. The bibliometric visualization maps were created using VOSviewer program (1.6.20), a commonly used program in bibliometric studies [ 41 ].

To assess the scientific impact of publications, citation analysis was performed on the retrieved dataset. Citation metrics, such as mean, median, range, and H-index, give insight into the influence and visibility of publications in the field. The H-index is defined as the highest number of publications (e.g. H) that have received at least H number of citations [ 42 ]. The citation analysis also included a comparison of the growth of citations with that of the number of publications with time to evaluate whether the increased research output corresponds to increase influence. Finally, the top 10 highly cited articles were also presented to highlight the foundational and influential papers in the field.

Two types of maps were created: co-authorship map and co-occurrence maps. The co-authorships maps were based on node size and color, with similar node color indicating close research collaboration. Similarly, keyword co-occurrence maps were constructed to identify clusters of frequently associated terms enabling thematic analysis of research foci. Each node in the map represents an entity (keyword or term), and the size of the node represents its frequency or weight, while links between the nodes reflect term co-occurrence relationships. Color-coded clusters illustrate thematic groupings, which were interpreted to identify dominant and emerging research domains [ 43 – 45 ]. Finally, an overlay visualization map was created to display how research keywords evolve over time. Unlike standard co-occurrence maps that only show relationships between terms. overlay maps add a temporal dimension by using color or gradient (e.g., blue versus yellow).

Results

Flow chart

Based on the search methodology, 1163 scientific documents were published between 2015 and 2024. Supplement 1 is the flow diagram for the steps in search strategy with the corresponding number of articles retrieved in each step.

Document type analysis

The analysis of document types showed that the majority of the publications, accounting for 64.7%, were full length research articles ( n = 752), underscoring the experimental and data driven nature of this scientific domain. Review articles made up 23.8% of the total ( n = 277). Letters (6.2%) and notes (3.5%) contributed to the literature with rapid and brief information. Editorials, conference papers and short surveys were minimally represented, each comprising less than 1% of the total output.

Language of publication

The linguistic distribution of the retrieved literature showed a clear dominance of the English language. Out of all the retrieved documents, 96.4% ( n = 1121) were published in English, the universal language of scientific communication. The most notable non-English languages were French (2.4%), German (1.5%), Chinese (0.7%), and Russian (0.4%). The remaining languages (e.g. Spanish, Italian, Japanese, Polish, Hungarian, Croatian) represent low and isolated national contributions. The total percentages of languages might exceed 100% because certain papers were bilingual and therefore counted twice.

Growth of publications and citations

Over the study period, a total of 1163 scientific documents were retrieved. No publications were retrieved on 2015 and 2016. The earliest documents on the topic were in 2017. The AAGR of publications from 2017 to 2024 was approximately 63.4% The retrieved publications collected 49,986 citations, an average of approximately 43 citations per article (95% CI = 35.9–62.3). Analysis showed that the median citation was 10 with positively skewed pattern (skewedness = 14.4). Therefore, a small number of highly cited articles are pulling the mean far above the central mass of the data. The range (0-4462) indicates substantial variability of citations for individual articles. In contrast to the wide range, the interquartile range was 31 indicating that most citation data lie within a narrow band, with just a very few high values inflating the mean and spread. Considering the relatively young age of the field, the obtained H-index value is relatively high (H-index = 103), suggesting that at least 103 publications in the dataset have each received at least 103 citations. Table 1 presents the number of publications and citations while Supplement II shows the annual linear growth of publications and citation over the study period.

Distribution of publications based on CAR-T cell products

Out of a total of 1163 retrieved articles on FDA-approved CAR-T cell products, tisa-cel was the most frequently investigated product accounting for 51.7% ( n = 601). Axi-cel followed closely with 554 (47.6%) publications, indicating nearly equal research interest in those two pioneering therapies. The remaining four products were represented at lower but notable frequencies: ide-cel appeared in 152 (13.1%) publications, liso-cel in 125 (10.7%), and cilta-cel in 120 (10.3%). Brexu-cel was the least represented with 106 (9.1%) publications.

Top cited articles

Analysis of the top 10 most cited articles revealed a correlation between clinical significance and citation density expressed as number of citations per year (Table 2 ). The articles were published between 2017 and 2022 in leading journals such as New England Journal of Medicine , The Lancet , and Journal of Clinical Oncology . The most influential studies addressed CD19-targeted CAR-T cell therapies for hematological malignancies [ 46 , 47 ]. Tisa-cel in pediatric acute lymphoblastic leukemia (ALL) and axi-cel in Large B-Cell Lymphoma demonstrated the highest annual citation rates (600.7 and 557.8 respectively), reflecting their role as first-in-class therapies. Follow up studies in Diffuse Large B-Cell Lymphoma (DLBCL), including those by Suchester et al. and Lock et al., further reported clinical efficacy and durability, each exceeding 290 citations per year [ 48 – 50 ]. A second group of highly cited studies focused on B-cell maturation antigen (BCMA)-directed therapies in multiple myeloma. Both ide-cel and cilta-cel showed higher citation rates (407.5 and 274 citations per year respectively), reinforcing the emerging role of CAR-T therapy in advanced multiple myeloma [ 51 , 52 ]. Notably, real-world validation studies and long-term safety analyses, provided essential translational insights [ 49 , 53 ], while a review on CAR-T toxicities received sustained attention (112.8 citations per year) highlighting ongoing clinical challenges [ 54 ].

Key contributors

The retrieved articles were disseminated through 333 different journals. The most prolific journal was Blood Advances ( n = 83; 7.1%), which focuses on translational haematology including emerging treatments of haematological cancers. The second ranking journal was Transplantation and Cellular Therapy ( n = 47; 4.0%). This journal is the official journal of the American Society for Transplantation and Cellular Therapy. Its scope specifically targets cell-based immunotherapies like CAR-T cell therapy. Table 3 shows the top 10 prolific journals in publishing papers on FDA-approved CAR-T cell products. Authors from at least 55 different countries participated in publishing the retrieved articles. The geographic distribution of publications is led decisively by the United States with 694 publications accounting for approximately 59.7% (Table 4 ). The proportion of internationally co-authored publications by the United States from its total publication in the field stands at 35.7% suggesting that the United States has a relatively high intra-country research collaboration. In contrast, European countries such as France, Germany, and Spain have different collaboration profile with limited intra-country research collaboration and high dependency on international research collaboration. The top prolific institutions in publishing scientific documents on FDA-approved CAR-T cells are the well-known national medical cancer centres known for their participation in clinical trials and collaboration with pharmaceutical industry. The University of Texas MD Anderson Cancer Center, with 132 publications, was the leading institutions, followed by Moffitt Cancer Centre, Memorial Sloan-Kettering Cancer Center, Pennsylvania State University, Dana-Farber Cancer Institute, Mayo Clinic, Stanford University, City of Hope National Medical Center, Cornell University. The top 10 active institutions are located in the United States. The Novartis International AG was among the top 10 active institution in the field.

Authorship metrics and network map

A total of 12,671 authors were found in the dataset, a mean of approximately 10.9 authors per article, indicating the tremendous collective and multicentre efforts required for developing and publishing innovative and translational clinical products. A striking number of the retrieved articles ( n = 792, 68.1%) had five or more authors per article. Figure 1 is a network visualization map of co-authorship for researchers with a minimum contribution of five publications. The map has 253 authors distributed across 13 clusters. Each cluster groups authors who frequently co-publish, suggesting close research collaboration, shared institutional affiliation, or shared thematic research focuses. The red cluster is the largest cluster ( n = 42) and represents research collaboration between academic institutions and pharmaceutical industry. The green and blue clusters are the second and the third largest clusters respectively. Both represent intra-national collaboration among different institutions in the United States.

Co-occurrence and overlay maps of author keywords

The co-occurrence and visualization maps of the 50 most frequent author keywords highlight both the scientific structure of the field and its chronological evolution. These maps provide insight into the dominant research topics and the progression of scientific focus over time. At the core of the co-occurrence map is the keyword “CAR-T” reflecting its centrality reflecting its centrality to all related research (Fig. 2 ). Closely linked are “immunotherapy”, “chimeric antigen receptor”, and “lymphoma”, which underscore the foundational role of immune-based strategies in targeting haematological malignancies. The presence of “cytokine release syndrome” (CRS) as a highly connected term points to a persistent focus on managing the unique toxicities associated with CAR-T cell therapies, particularly in clinical settings. A strong clinical orientation is evident from keywords such as tisa-cel, axi-cel, brexu-cel, and liso-cel, all of which are FDA approve CAR-T therapy products. These terms are often co-linked with specific keywords ALL and DLBCL reflecting the therapeutic indications for which these products were first introduced and evaluated. The emergence of “multiple myeloma”, “BCMA”, and “ide-cel” in a distinct cluster suggests a recent shift in focus toward next generation targets and the expansion of CAR-T indications. These keywords highlight the transition from CD19-focused therapies to those targeting BCMA in plasma cell malignancies. The presence of celta-cel further emphasizes this. The overlay visualization map adds temporal dimension to the keyword co-occurrence map, where earlier studies (darker nodes) focused on “tisa-cel”, “leukemia”, and “Chimeric Antigen Receptor”. In contrast, recent terms (yellow nodes), such as “multiple myeloma”, “BCMA”, “ide-cel”, and “cost-effectiveness” indicate evolving research interest in expanding indications and assessing economic viability (Fig. 3 ).

Co-occurrence map of most frequent terms in abstract

Analysis of t co-occurrence the most frequent 500 terms present in abstracts of the retrieved dataset showed the following four major thematic clusters, each representing a distinct research focus within the field (Fig. 4 ). The green cluster encompasses terms such as receptor , leukemia , antigen , development , target , gene therapy , and Kymirah reflecting a strong emphasis on the molecular and therapeutic development of CAR-T constructs. This cluster highlights literature focused on the immunological mechanism of action, antigen recognition (BCMA, and CD19) and the evolution of CAR-T design. Regulatory references like FDA and drug administration indicate that many studies within this group also address the translation of CAR-T therapies from bench to bedside including their clinical approval pathways and real-world development. In contrast, the red cluster is dominated by clinical outcome-oriented terms such as median , ORR (overall response rate) , CRS , hazard ratio , lymphodepletion , and names of pivotal trials such as ZUMA and JULIET. This cluster captures the clinical trial literature that evaluates efficacy endpoints, treatment-related toxicities, and survival metrics. It reflects the intensive investigation into safety profiles, particularly like CRS and immune effector cell-associated neurotoxicity syndrome (ICANS), which have shaped the treatment protocols. The blue cluster brings focus to the economic and policy dimension of CAR-T therapy. Frequent terms such as cost, model, quality, cost-effectiveness, threshold, and uncertainty point to studies conducting health technology assessment, economic modelling, and budget impact analysis. These studies explore the value proposition of CAR-Ts, reflecting the growing concern over their affordability and sustainability in the healthcare system. Lastly, the yellow cluster is centered around the emerging therapeutic space of BCMA-targeted CAR-T therapies in multiple myeloma. Terms like BCMA, ide-cel, plasma cells, multiple myeloma, and monoclonal antibody identified this cluster as focused on novel targets beyond CD19. It highlights recent advancement in treating relapsed and refractor multiple myeloma using agents such as ide-cel and related constructs.

Discussion

The current study offers a comprehensive overview of the research landscape surrounding FDA-approved CAR-T cell therapies. To date, six CAR-T cell therapies have received FDA approval, each made a significant advancement to cancer immunotherapy. The six different products differ in their indications, design, toxicity profile, and manufacturer, yet al.l harness engineered T cells to eliminate malignant cells. Tisa-cel, by Novartis, was the first FDA approved CAR-T cell therapy indicated for pediatric B-ALL and adult DLBCL [ 47 , 55 – 57 ]. The tisa-cel employs a 4-1BB co-stimulatory domain promoting T cell activity with comparatively moderate toxicity. Axi-cel and brexu-cel, both from Kite Pharma, use CD28 co-stimulation yielding rapid responses in aggressive lymphomas and leukemias, though often associated with higher rates of CRS and ICANS [ 46 , 50 , 54 , 58 – 64 ]. In contrast, liso-cel (Bristol Meyers Squibb) features a controlled CD4/CD8 composition and shows a favourable safety profile in DLBCL [ 65 – 69 ]. The dominance of tisa-cel and axi-cel in the retrieved literature is expected given their early FDA approval in 2017 and their role in establishing CAR-T cell therapy as a viable clinical modality. With the approval of ide-cel and cilta cel for the treatment of multiple myeloma, by targeting BCMA, the research in the field has expanded and achieved high AAGR with time. Both ide-cel and cilta-cel showed high efficacy, but challenged with prolonged cytopenias and neurotoxicity [ 70 , 71 ]. The expanded therapeutic indications to include relapsing multiple myeloma contributed to growth of publications and citations.

Co-occurrence map showed that one of the prominent keywords closely related to FDA-approved CAR-T products were CRS and neurotoxicity. CRS is a systematic inflammatory response triggered by robust T cell activation and expansion following target engagement [ 72 – 74 ]. This leads to the release of high levels of proinflammatory cytokines such as IL6, INF-γ, and INF-α. Clinically CRS manifest as fever, hypotension, hypoxia, and in sever cases, multi-organ dysfunction. Neurotoxicity, ICANS, caused by CAR-T cell products manifest as neuroinflammation in the central nervous system leading to confusion, cerebral edema and seizures [ 75 – 78 ]. Different CAR-T products have different toxicity profile. Products incorporating CD-28 co-stimulatory domains, namely axi-cel and brexu-cel, are associated with higher rates and earlier onset of CRS and ICANS [ 75 , 79 – 82 ]. Conversely, products utilizing 1-4BB co-stimulatory domain, such as tisa-cel, liso-cel, ide-cel, and cilta-cel, exhibit slower T cell expansion kinetics and lower toxicity rates. Cilta-cel, when used for multiple myeloma, has been associated with delayed neurotoxicity with movement and neurocognitive symptoms. Tocilizumab (IL6 receptor antagonist) has been used to prevent CRS in high risk patients while corticosteroids, not IL6 receptor antagonist, have been the primary preventive measure for ICANS.

The thematic analysis of the retrieved documents demonstrated that one of the emerging themes in the field is the cost-effectiveness of CAR-T cell products. These innovative treatments are associated with extra-ordinary upfront cost ranging from 300,000 to 400,000 USD per treatment course [ 83 – 86 ]. Despite high cost, several economic evaluations have demonstrated that CAR-T cell therapies may be cost-effective under specific assumptions, particularly for patients with few remaining therapeutic options [ 87 – 89 ]. In terms of clinical effectiveness, CAR-T cell therapies have shown remarkable efficacy across hematologic malignancies [ 49 , 51 , 90 ]. A study evaluated anti-BCMA CAR-T therapy for patients with relapsed or refractory multiple myeloma and found it to be a cost-effective alternative to standard treatment, offering a favorable balance between clinical benefit and economic impact [ 91 ]. Similarly, a second study assessed liso-cel, a CD19 directed CAR-T therapy as a second line treatment for relapsed or refractory DLBCL. The findings demonstrated that liso-cel is cost-effective with cost-effectiveness ratios of 99,669 USD from a healthcare perspective and 68,212 USD from a societal perspective [ 92 ].

While current FDA-approved CAR-T cell products primarily target hematological malignancies, expanding research efforts to include solid tumors remains a major future goal. This involves overcoming major key challenges such as tumor antigen heterogeneity, immunosuppressive microenvironments, and limited T cell infiltration. Investment in pre-clinical models, antigen discovery platforms, and 4th and 5th generation CAR-T constructs, such as cytokine secreting cells, may enable the translation of CAR-T therapy to solid tumors [ 13 , 93 – 95 ].

The dominance of the United States in the field aligns with previously published studies on the leading role of the United States in oncology, haematology, and immunology [ 96 – 98 ]. The higher dependency of European countries on international research collaboration with researchers in the United States highlights a need for capacity building initiatives to expand autonomous CAR-T development programs within Europe. There is also an urgent need to establish dedicated CAR-T cell research and treatment centers in low- and middle-income countries (LMIC) to ensure global equity in access to advanced cancer care. These centers would serve as hubs for clinical trials, manufacturing, and real-world data collection in diverse populations. By replicating the infrastructure and regulatory models adopted in high-income countries, LMIC can begin to bridge the gap in precision oncology and contribute meaningfully to global CAR-T cell research network. This requires training and empowering scientists and clinicians from different world regions. This includes specialized educational programs in genetic engineering, immunology, and cellular manufacturing, as well as clinical fellowship in CAR-T trial sites. International collaboration programs and public-private relationships could fund exchange initiatives to expose early career researchers from LMIC to CAR-T development and deployment. Such efforts would not only build local capacity, but also enhance the cultural and biological diversity of CAR-T research, which is crucial for translational robustness.

The findings that research on FDA-approved CAR-T cell therapy has a mean of approximately 11 authors per article reflects the complex nature and multidisciplinary aspects of multicentred, large scale, and long follow up clinical trials and investigations regarding CAR-T cell therapy. Therefore, future clinicians and researchers must be equipped with foundational knowledge in immunogenetics, cell signalling, and genome editing. Updating curricula to include hands on training in cellular manipulation, immune monitoring, and translational trial design will foster a generation of professionals capable of leading innovation in cell-based oncology.

The current bibliometric analysis presents a novel and clinically grounded contribution to the growing body of literature surrounding CAR-T therapy, with a specific focus on FDA-approved products. A major strength of the current study lies in the exclusive focus on market-authorized CAR-T cell therapies. While previous bibliometric analyses have typically taken a broader approach, encompassing experimental constructs, early-phase clinical trials, and both hematologic and solid tumors, the current study isolates research related to FDA-approved CAR-T products. By concentrating on approved agents, the analysis provides a clinically actionable overview of research trends in therapies that are actively implemented in routine practice. This level of specificity enhances the real-world applicability of the findings and aligns more closely with translational and policy-level decision-making. In addition, the study adopts a product-specific analytical approach, disaggregating publication patterns and citation impact by individual CAR-T product. This allows for insights into how the scientific community has engaged with each therapy over time. Unlike other studies that aggregate CAR-T research into a single undifferentiated domain, this disaggregation enables the identification of distinct developmental trajectories across products.

While it is accurate that there are currently six FDA-approved CAR-T cell products to date, this narrow approval set is precisely what underpins the novelty and strategic value of the current study. The strength of our work lies in its comprehensive analysis of the evolving scientific literature. The obtained bibliometric insights are no assumptions but data driven, which adds significant novelty and utility to the current literature especially for non-clinical stakeholders, policy makers, and early career scientists entering the field.

Limitations

Despite these strengths, several limitations should be acknowledged. The reliance on a single database-Scopus-while justified by its comprehensive citation coverage, inherently excludes literature indexed solely in other databases such as Web of Science, PubMed, or Embase. This may result in the under-representation of certain regional publications or niche research communities. Furthermore, the title search strategy, though designed for precision, may miss relevant studies in which key terms are embedded only in the full text or use non-standard nomenclature. Such omission could bias thematic findings or affect comparative product assessments. Like all citation-based analyses, the current study is subject to time-dependent citation bias. Older articles inherently have more time to accumulate citations, potentially skewing influence metrics in favor of earlier FDA-approved products. In addition, non-English language publications were excluded, which may affect the comprehensiveness of international research representation, especially from high-output countries like China, Japan, and Germany.

Another methodological limitation relates to overlapping indications and trial reporting. Some publications discuss multiple CAR-T products or report pooled outcomes, making product-specific attribution complex. Similarly, the exclusion of conference abstracts-many of which report critical preliminary data – may delay the recognition of emerging therapeutic directions and innovation milestones. It is also important to note that bibliometric analysis, by nature, is quantitative and structural rather that qualitative or clinical. While it captures research volume, network strength, and citation trends, it does no evaluate the quality of clinical outcomes, safety profiles, or patient-centred measures that are essential in fully appraising therapeutic value.

Conclusions

This bibliometric and knowledge-map analysis provides a comprehensive and data-driven portrait of evolving research landscape on FDA-approved CAR-T cell products. By exclusively focusing on market-authorized products, this study offers a uniquely clinically relevant and translationally aligned overview of a rapidly expanding domain in hematologic oncology. The results demonstrate that research on approved CAR-T cell products has undergone an extra-ordinary surge in scholarly output, marked by high AAGR, increasing international collaboration, and strong citation metrics that reflect both foundational discoveries and sustained research interest. The thematic analysis reveals that the field has matured from proof-of-concept studies involving CD19 targeted therapies, such as tisa-cel and axi-cel, toward more sophisticated inquiries involving BCMA-targeted agents like ide-cel and cilta-cel. These newer agents have become the subject of intense investigations, particularly in the treatment of recurrent multiple myeloma, a setting previously marked by limited therapeutic options and poor prognosis. The emergence of these agents has spurred research not only into efficacy and safety but also into real-world implementation, economic sustainability, and long-term outcomes. One of the most important and forward-looking themes identified in this study is the rise of cost-effectiveness analyses. As CAR-T cell therapies carry considerable upfront costs, recent research has identified has shifted to evaluating their economic value in relation to survival benefits, quality-adjusted life years and healthcare system sustainability. These evaluations are essential in guiding reimbursement decisions and shaping equitable CAR-T cell therapies across different healthcare systems and regions. Furthermore, the field continues to face important challenges related to toxicity management. These adverse events have driven the development of standardized grading systems and early intervention strategies, along with efforts to engineer safer next generation CAR constructs. The literature reflects growing interest in clinical trial design optimization, comparative efficacy studies using real-world data, and the integration of CAR-T therapies into earlier lines of treatment. Scientifically, this study underscores collaborative and multidisciplinary research. Leading institutions and authors, in collaboration with pharmaceutical industry, have driven innovation, conducted pivotal trials, and contributed to regulator success. The United States stands out as a central hub in the global CAR-T research ecosystem, although Europe and other regions are progressively increasing their presence and impact through partnerships.

In summary, this study offers a focused, methodologically rigorous, and clinically meaningful bibliometric evaluation of FDA-approved CAR-T cell therapies, a field at the intersection of precision medicine, immune therapy, system-level health policy. By identifying key actors, research trends, and evolving thematic priorities-particularly the rise of economic evaluation-this work contributes significantly to understanding the structure, growth, and future directions of this rapidly advancing field.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1. Flow diagram of the search strategy.

Supplementary Material 2.

Acknowledgements

The authors acknowledge the use of AI in language editing only. No results or data were obtained or generated by any type of AI.

Author contributions

M.S started the ide, did the analysis, and wrote the manuscript.

Funding

No funding was received to assist with the preparation of this manuscript.

Data availability

All data, including the search query, are available and can be provided upon personal request from the authors.

Declarations

Ethics approval and consent to participate

Not applicable. No IRB was required for the current study since all data were obtained from Scopus database and no patients or human subjects were involved directly in the study. No humans or animals or any biological samples were involved in the current study and therefore no consent to participate were collected.

Consent for publication

Not applicable. This study did not involve any individual person’s data in any form (including individual’s details, Figures, Diagrams, Videos, Images) and therefor consent to publish was not required.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Associated Data

Data Citations

Miao L, Zhang J, Zhang Z, Wang S, Tang F, Teng M, et al. A Bibliometric and Knowledge-Map Analysis of CAR-T Cells From 2009 to 2021. Front Immunol. 2022;13:840956. 10.3389/fimmu.2022.840956. Epub 20220318.

Supplementary Materials

Supplementary Material 1. Flow diagram of the search strategy.

Supplementary Material 2.

Data Availability Statement

All data, including the search query, are available and can be provided upon personal request from the authors.