Antibody-Drug Conjugates: Pharmacotherapeutic Properties and Future Perspectives.

1. Introduction

Cancer remains one of the most devastating diseases worldwide, not only because of its high mortality and morbidity, but also due to the emotional and financial burdens it places on patients, families, and healthcare systems. Although major advances have been made in cancer research, current treatments are mostly ineffective, leading to poor prognosis and disease management. In addition, they are frequently associated with significant undesirable effects that further reduce the quality of life of patients and entail high costs due to drug pricing and the need for repeated administrations [ 1 , 2 ]. Over the years, new cancer therapies have been developed to address the limitations of existing treatments. For example, targeted therapies with antibody–drug conjugates (ADCs) emerged as an innovative way of delivering highly cytotoxic agents, also known as payloads, by taking advantage of the selectivity of certain antibodies to specific receptors that are overly expressed on the surface of cancer cells when compared to their healthy counterparts [ 3 , 4 ]. Although this approach to targeted therapies was first conceptualized in the 60s, based on the “magic bullet” concept of Paul Ehrlich, it was only during the year 2000 that the first ADC (gemtuzumab ozogamicin) obtained its market approval for clinical use [ 5 ]. Structurally, ADCs are composed of three main components [ 6 ]: (i) an antibody moiety responsible for directing the ADC to the targeted cells, promoting the internalization of the ADC upon interacting with its complementary cell surface receptor or, if not internalized, stimulating the activation of the immune system via antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC); (ii) a certain number of payloads (commonly between two to eight) that induce cell death through their specific mechanisms of action (e.g., they can act as mitotic inhibitors, topoisomerase I inhibitors, or damaging the genetic material of cancer cells); and (iii) a certain number of linkers (equal to the number of payloads) responsible for maintaining the payloads covalently bound to the antibody moiety and for promoting their rapid release whenever the original ADC is exposed to certain chemical or enzymatic stimuli that are frequently found within tumoral microenvironments or inside cancer cells.

The concept of using ADCs to treat some types of cancer seems very promising, as patients can be submitted to highly effective treatments, like the ones used in conventional chemotherapy, while minimizing the risk of adverse side effects, since ADCs use antibody moieties that are very selective to a tumor-associated antigens (TAA), like the ones used in immunotherapies with monoclonal antibodies (mAbs) or, ideally, to a tumor-specific antigen (TSA) [ 7 ]. However, the collected evidence has shown that ADCs still exhibit some limitations that need to be addressed in order to optimize their efficacy/effectiveness and safety profiles [ 8 ]. Considering the aforementioned information, this review aims to provide a summarized overview of ADC pharmacotherapy, outline the current limitations restricting their optimal use, explore novel strategies addressing these challenges, and examine emerging therapeutic applications. To achieve these objectives, the methodology adopted in this article involved a bibliographic review of the available scientific literature on topics related to ADC-based targeted therapies. The information required to elaborate this review was mostly obtained from a few searchable bibliographic online databases (like PubMed ® and ScienceDirect ® ), books, e-books, and other kinds of documents published by international health societies and regulatory agencies. During the research phase, some of the terms inserted in the query box included “Antibody-Drug Conjugate*”, “Mechanism of Action[MeSH Terms]”, “Pharmacotherapy[MeSH Terms]”, “Pharmacovigilance[MeSH Terms]”, “Adverse Drug Reaction[MeSH Terms]”, “Limitation* OR Challenge*”, and “Future Perspective* OR Future Prospect*”.

2. Pharmacotherapy of ADCs

ADCs are a specialized group of biopharmaceutical products that belong to the family of targeted therapeutic agents for the treatment of cancer. As previously mentioned, they were introduced into the clinical setting to overcome the toxicity issues associated with the use of conventional chemotherapy, as well as the susceptibility for the development of drug resistance of immunotherapy with mAbs, by combining the two most favorable attributes of each of these types of cancer treatments [ 6 ]. For instance, brentuximab vedotin, an ADC used to treat stage III/IV Hodgkin’s lymphoma obtained a 2-year modified progression-free survival (PFS) of 82.1%, when compared to 77.2% with standard adriamicyn, bleomycin, vinblastine, and dacarbazine, while having a hazard ratio (HR) of 0.77 when compared to the same standard-of-care treatment [ 9 , 10 ]. For non-hematologic malignancies, trastuzumab emtansine, for example, extended the median overall survival (OS) to 30.9 months compared to 25.1 months with standard-of-care treatment and an HR of 0.68 in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer [ 10 , 11 ]. In terms of biological activity, ADCs can exert multiple mechanisms of action. They can act similarly to mAbs by either inducing the activation of the immune system (via ADCC, ADCP, or CDC) or by blocking the signaling transduction pathways of some surface receptors involved in the proliferation of malignant cells [ 12 ]. Moreover, ADCs also possess a mechanism of action that is unique to this class of targeted therapies [ 13 ]: (i) first, the antibody moiety binds to overexpressed or specific receptors that are present on the surface of targeted cells; (ii) the interaction creates signals in the cell to internalize the newly formed ADC–antigen complex via endocytosis; (iii) the resulting endosome then fuses with a lysosome, forming an endolysosome where the internalized ADC is going to be digested, releasing the payloads from the antibody moiety through a specific release mechanism that is correlated with the type of linker used. For instance, while acid-sensitive cleavable linkers depend on the presence of lower pH values within the endolysosome to release the payloads, glutathione-sensitive disulfide linkers rely on the presence of intracellular reducing agents, such as glutathione (whose levels are typically elevated in malignant cells), to promote the release of these cytotoxic agents. Linkers can also be classified as enzymatically cleavable linkers (if they release the payloads in the presence of specific hydrolytic enzymes, particularly those that are found inside the endolysosomal lumen) or as non-cleavable linkers (if the payload release relies on the complete degradation of the antibody moiety); (iv) once released from the digested ADC, payloads leave the endolysosome and reach their specific intracellular target where they will exert their unique mechanisms of action and induce the death of targeted cells; and (v) due to their small, apolar, and uncharged molecular structure, some payloads can passively diffuse across cellular membranes, enabling them to enter the cytoplasm of adjacent tumor cells and produce a bystander killing effect, ensuring that multiple cancer cells are effectively killed, even in highly heterogeneous tumors and/or with low rates of internalization [ 14 ]. Figure 1 depicts a schematic representation of the multiple mechanisms of action that current ADCs can exert on tumoral cells. However, it does not account for several factors that can substantially impact their clinical effectiveness in real-world settings. For instance, while the figure suggests an equal (1:1) distribution between the primary and alternative mechanisms of action, in reality, only about 1–2% of administered ADCs reach, and are internalized by, the targeted tumor cells [ 3 ]. This limited uptake can be attributed to variability among tumor cells, even within the same cancer type, in terms of target antigen expression, as well as endocytic and intracellular trafficking pathways, all of which can directly affect the therapeutic response [ 15 ]. Furthermore, heterogeneity in ADC-related properties, such as the drug-to-antibody ratio (DAR, the average number of payloads per antibody moiety), can contribute to differences in clinical efficacy, as ADCs with higher DARs generally show greater therapeutic activity but also carry an increased risk of adverse effects [ 16 ].

The introduction of ADCs into the drug market was initially hindered by their structural complexity and the limited clinical benefit observed in early studies [ 17 ]. However, their clinical implementation has accelerated in recent years, partly driven by the need for improved therapeutic responses in cancers where mAb-based immunotherapies have shown limited effectiveness [ 18 ]. By the end of 2025, there was a total of twenty-one ADCs approved globally for clinical use. Of these, twenty retained their marketing authorizations at that time, while only moxetumomab pasudotox had been withdrawn from the market due to commercial reasons unrelated to its safety or efficacy. According to their therapeutic applications, ADCs can be divided into those used in hematologic malignancies or those used in non-hematologic malignancies [ 6 ]. Table 1 summarizes the most important characteristics regarding molecular composition and the main pharmacotherapeutic indications of the previously mentioned twenty-one ADCs ever approved in at least one of the major drug markets by the end of 2025. Data were extracted from both regulatory documents and the published literature. When discrepancies were identified between these two sources of information, priority was given to the most authoritative source, i.e., the regulatory documents. However, when relevant data were not available in regulatory documentation, information was supplemented from the scientific literature. Potential off-label uses were not considered. Table 2 , on the other hand, summarizes the most relevant undesirable effects, drug interactions, effects on fertility, pregnancy, and lactation, alongside the most important precautions and contraindications of the ADCs previously mentioned in Table 1 . The data were extracted based on the same search strategy as the one used to collect the data presented in Table 1 .

3. Current Limitations

Although the introduction of ADCs into the clinical setting has brought several promising therapeutic advantages, particularly in relapsed, refractory, and metastatic cancers, there are still some drawbacks that need to be addressed in order to design and develop new ADCs with optimized chemical and biological properties. Some of these limitations include: (i) toxicity; (ii) susceptibility to the development of drug resistances; (iii) complex pharmacokinetic profiles; and (iv) stability issues.

Even though ADCs were conceptualized with the intent of overcoming the toxicity issues associated with the use of conventional chemotherapy (which was achieved, to a certain extent), they still retain a suboptimal safety profile, mainly attributed to the emergence of off-target toxicities related to the untimely release of payloads into the bloodstream instead of at the actual site of the tumor(s) [ 102 ]. This phenomenon is typically associated with the use of cleavable linkers that are susceptible to release of the payloads when they are exposed to certain chemical or enzymatic stimuli that are exacerbated within tumoral microenvironments and inside cancer cells but are also present in normal physiological conditions, although to a lower extent [ 103 ]. Other causes of off-target toxicity may involve the excessive bystander killing effect and the non-specific uptake of these drugs by healthy cells. For instance, the temporary withdrawal of belantamab mafodotin, an ADC bearing a non-cleavable linker, was partially associated with the excessive uptake of this drug by the corneal epithelial cells and due to the incapacity of the charged amino acid–linker–payload complex that is released from the antibody moiety to diffuse out of these cells, resulting in the emergence of frequent episodes of ocular toxicity [ 104 ]. It is worth mentioning that on-target toxicity issues may also occur with this type of targeted therapy, because until now, every antibody moiety used in currently market-approved ADCs can only target TAAs instead of TSAs [ 6 ]. In addition to the toxicity issues correlated with the cytotoxicity of the payloads used in this kind of targeted therapy, the risk of unwanted immunogenicity is another issue that is observed with the use of biologic drugs, including ADCs [ 105 ].

A major limitation associated with the use of targeted therapies is their susceptibility to drug resistances developed by cancer cells. Although ADCs were (in part) introduced into the market to overcome resistances that rapidly emerged with other treatments, such as mAb-based immunotherapies, clinical evidence indicates that resistance to ADCs can also occur [ 106 ]: (i) antigen–antibody-mediated drug resistances are a group of resistances that negatively impair the effectiveness of antibody-based therapies by reducing the expression of targeted antigens on cancer cells, increasing receptor degradation, altering receptor structure, and/or by decreasing antigen–antibody affinity [ 106 , 107 , 108 ]; (ii) upon binding the antibody moiety to its corresponding receptor, ADCs should be internalized into the targeted cell via receptor-mediated endocytosis. However, in this step, tumoral cells may develop mechanisms of decreased internalization efficiency and/or induce alterations in the endosomal transport pathways of ADCs, preventing them from exerting their expected efficacy [ 106 , 107 , 109 ]; (iii) lysosomal degradation can also contribute to drug resistance by blocking the release of payloads from ADCs and preventing their exit from the endolysosomal lumen. For example, elevated endolysosomal pH can hinder ADCs with non-cleavable and acid-labile linkers from releasing their cytotoxic agents and impede the diffusion of weakly acidic payloads into the cytosol [ 106 ]. Conversely, lowered pH may prevent hydrophobic weak-base payloads from reaching the cytosol [ 110 ]. Moreover, reduced expression of the lysosomal membrane protein solute carrier family 46 member 3 (SLC46A3) has been associated with decreased payload release from ADCs bearing non-cleavable linkers such as those derived from maytansine and SG3376 [ 106 , 111 ]; (iv) even if the payloads are released from the ADC and from the endolysosome, it is still possible for the targeted cell to develop resistances to the payloads themselves, similar to what is observed with the use of conventional chemotherapy. Genetic mutations, decreased expression rates of susceptible intracellular targets, increased expression rates of resistant isoforms, post-translational modifications to the targets, and upregulation of the adenosine triphosphate (ATP)-binding cassette efflux transporters are examples of payload-related drug resistance mechanisms that may arise with the use of ADCs [ 109 , 112 ]; (v) tumor cells can increase survival by exploiting redundancy in receptor tyrosine kinase signaling, altering cell-cycle dynamics (particularly relevant for cell-cycle dependent payloads), upregulating cytoprotective proteins, and downregulating pro-apoptotic proteins, thereby reducing the efficacy of ADCs and other cancer therapies [ 106 , 107 , 113 ]; and (vi) in addition to the resistance mechanisms that can emerge from individual cells, the tumoral microenvironment where these cells reside may also be involved in further drug resistance, as they possess immunosuppressive properties and have poor accessibility that can hinder the penetration of antibody-based therapies because of the large molecular size of these drugs and due to the elevated interstitial fluid pressure created within tumoral microenvironments, which neutralizes the pressure gradient needed for drugs to leave the bloodstream and reach the tissues [ 114 ].

In addition to the primary limitations, ADCs exhibit a complex pharmacokinetic profile that makes it difficult to predict their behavior inside the body and, consequently, adjust the dosing to each individual patient. Unlike other drugs, the pharmacokinetic profile of ADCs requires measuring not only the concentration of intact ADCs (antibody moieties and conjugated payloads) but also non-conjugated antibody moieties, unconjugated payloads, and their metabolites in the bloodstream to predict therapeutic efficacy and toxicity risk [ 115 ]. Moreover, ADCs face an increased likelihood of aggregation, even more than mAb therapies, since the hydrophobic nature of the attached payloads might facilitate the exposure of aggregation-prone regions and induce the formation of strong inter-molecular interactions with other protein-based drugs [ 116 ]. The formed aggregates not only prevent the sequestered molecules from binding to their intended targets and exerting their expected mechanism of action; however, they can also trigger unwanted immune reactions and increase the risk of off-target payload release into the bloodstream, reducing efficacy and raising safety concerns at the same time with the use of ADCs [ 116 ].

4. Novel Approaches to the Concept of ADC and New Therapeutic Applications

The introduction of ADCs revolutionized targeted therapies for cancer by leveraging the selectivity of mAbs to deliver potent cytotoxic agents directly to cancer cells, offering therapeutic advantages over other treatments. However, clinical use has revealed limitations that must be addressed to enhance the efficacy and safety of future ADCs. Key proposed improvements for next-generation ADC design and development include the following aspects [ 117 ]: (i) better tumor penetration capacity; (ii) improved microenvironment targeting activity, instead of just targeting individual tumoral cells; (iii) flexibility to comprise novel payloads with new mechanisms of action and innovative approaches that promote enhanced activity against tumoral cells, while causing minimal damages to healthy cells; (iv) adjustable linker chemistry and its conjugation techniques, which should be improved to prevent the premature discharge of payloads into the bloodstream, whilst facilitating their release inside cancer cells or within tumoral microenvironments; (v) reduced risk of unwanted immunogenicity and on-target toxicity caused by the antibody moiety; and (vi) enhanced internalization trafficking and capacity to target multiple and, preferably, highly conserved cellular structures within tumoral cells.

As was previously mentioned, one of the main limitations with the use of large biomolecules in the treatment of solid tumors is their accessibility, especially to deeper cells within the tumoral microenvironments. Instead of using a fully assembled antibody moiety, it is possible to enhance the penetration capacity of ADCs by using smaller molecules or antibody derivatives that can still interact with similar selectivity to their complementary targets, when compared to their fully assembled counterparts [ 13 ]. Furthermore, using smaller molecules or antibody fragments can significantly reduce the production cost and complexity of these types of drugs, as they could be produced in microbial expression systems instead of using mammalian expression systems, allowing for the fragments to be produced more quickly and at higher yield rates [ 118 ]. In addition, smaller molecules (e.g., aptamers, peptides, and other small-molecule linkers) or antibody fragments can substantially decrease the potential risk of unwanted immunogenicity, as they possess fewer domains recognizable by the immune system [ 118 , 119 ]. However, smaller formats can also exhibit altered pharmacokinetics, including reduced circulation half-life; the absence of a fragment crystallizable (Fc) region in these fragments prevents the activation of immune effector functions (e.g., ADCC, ADCP, and CDC) [ 120 , 121 ]. Examples of some novel alternatives to ADCs using antibody fragments and smaller molecules include the fragment antigen-binding (Fab)-drug conjugate (a type of ADC comprising just one of two Fab regions of an antibody, instead of using the entire molecular structure of the antibody), the single-chain variable fragment (scFv)–drug conjugate (a conjugate-based drug incorporating a fragment containing the variable region of one heavy and one light chain connected by a peptide linker with 15–20 amino acids), the nanobody–drug conjugate (a small conjugated drug that uses the variable domain of a single antibody heavy chain instead of the entire antibody), and the aptamer–drug conjugate (which, instead of using an antibody derivative, uses a single-stranded oligonucleotide that folds on its own to acquire a unique three-dimensional structure, enabling it to bind to specific targets with high affinity and specificity) [ 122 , 123 ]. Another approach is the use of heavy-chain ADCs, where the antibody moiety is modified to lack the two light chains and the first constant domain of each heavy chain. While this novel alternative shows limited improvement in penetration capacity, compared to other drug conjugation strategies, heavy-chain ADCs are unique in their ability to activate the immune system, given the presence of the Fc region [ 124 ]. Figure 2 shows a schematic representation of the novel approaches that have been considered to overcome the poor penetration capacity of ADCs in solid tumors.

Tumoral microenvironments are known to be enriched with various types of proteases, such as matrix metalloproteases and serine proteases, that can be used to enhance the selectivity of antibody moieties that target TAAs [ 125 ]. One such strategy involves protecting the antigen-binding sites of the antibody moiety with small masking peptides that are covalently bound to the antibody on each antigen-binding site through a cleavable linker sensitive to these proteases [ 126 ]. Upon reaching the protease-enriched medium of tumoral microenvironments, the protease-sensitive linkers are cleaved, and the masking peptides are released from the antibody, restoring the availability of the antigen-binding sites. This allows probody–drug conjugates ( Figure 3 ) to remain inactive in circulation, preventing them from interacting with the membrane receptors of healthy cells, ensuring that the probody is only going to be bioactivated near tumoral cells [ 126 ].

Future improvements to antibody moieties in ADCs should focus on enhancing the penetration of large biomolecules, while optimizing the overall therapeutic efficacy and safety of this component. For instance, by using bispecific antibodies ( Figure 3 ) it is possible to overcome some safety concerns related to on-target toxicity, as they can target two distinct TAAs that, ideally, are not present simultaneously on healthy cells but coexist on tumor cells, enabling selective internalization or activation of the immune system only when both antigen-binding sites interact with their respective targets [ 127 ]. Antibody moieties that interact with highly conserved structures that are less likely to undergo molecular alteration have a lower probability to fall prey to the development of drug resistance [ 128 ]. Engineering the Fc region can also be considered to enhance Fc-mediated effectors functions and to optimize the structure of the antibody moiety, so the latter can act as an independent drug. Therefore, the original ADC becomes less dependent on the cytotoxicity of the small fraction of payloads that are internalized to exert an effective therapeutic response [ 129 ]. Beyond what was previously stated, the use of human-derived antibodies should be taken into account to reduce the risk of unwanted immunogenicity associated with the use of non-human antibodies [ 117 ].

Most adverse drug reactions associated with ADCs arise from the on- and off-target cytotoxicity of payloads to healthy cells. On-target toxicity is primarily due to antibody moieties binding to TAAs on healthy cell membranes, while off-target toxicity is often linked to linker instability, leading to premature payload release into the bloodstream. Additionally, payload chemistry plays a significant role [ 103 ]. Excessive hydrophobicity can increase aggregation, immunogenicity, and unwanted diffusion to healthy cells, while high hydrophilicity may prevent effective bystander killing of receptor-negative cancer cells [ 103 ]. In addition, novel payloads need to overcome drug resistance [ 106 ]. Some of the most innovative developments proposed for new payloads include the use of multiple payloads with different intracellular mechanisms of action and the exploitation of new types of payloads, such as, for example, immune stimulator compounds used as agonists of stimulator of interferon genes (STING) and toll-like receptors (TLRs), two crucial receptors involved in the activation of the innate immune system [ 130 ]. The use of antisense oligonucleotides (short sequences of single-stranded deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) designed to bind to specific messenger RNA (mRNA) sequences in order to alter the mRNA involved in the pathogenesis of the disease and modulate protein expression through several distinct biological mechanisms) have also been considered, as well as the use of radionuclides and protein degraders such as proteolysis targeting chimeras (PROTACs, a type of heterobifunctional molecules containing a protein-of-interest binding domain connected to an E3 ubiquitin ligand by a linker. PROTACs target specific proteins to be degraded by taking advantage of the ubiquitin–protease system to bring together the target protein and an E3 ligase) [ 131 , 132 , 133 ]. Figure 3 provides a schematic representation of some of these novel approaches to the development of future payloads.

Finally, the linker chemistry is another critical factor involved in both the safety and efficacy of ADCs. As mentioned earlier, premature off-target release, caused by poor linker stability, is a major factor in ADC toxicity. However, the aggregation phenomena that is associated with decreased serum stability is closely correlated with the conjugation technique used to bind the payloads to the antibody moiety [ 134 ]. For instance, while low DARs are linked to reduced therapeutic outcomes, ADCs with high DARs tend to exhibit stability issues, potentially resulting in the premature release of conjugated payloads, increasing the risk of off-target toxicity [ 6 ]. To address the limitations of current linkers, it is important to improve their stability in solution and ensure a rapid payload release only when they are exposed to unique chemical or enzymatic triggers solely found inside cancer cells and within their microenvironments. Additionally, innovative controlled homogenous conjugation techniques can help to produce more uniform molecules with better DAR values and a more predictable pharmacokinetic behavior, while maintaining the antibody’s integrity [ 135 ]. Examples of such techniques include the engineered amino acid approaches (which use engineered cysteines and non-natural amino acids) ( Figure 4 ), enzyme-mediated approaches (with transglutaminase, formylglycine-generating enzyme, sortase A, glycotransferases, and endoglycosidase), and linker-based approaches (with dibromopyridazinediones, dibromomaleimides and other enhanced maleimides, with hydrophilic linkers, and/or with bis-alkylating linkers) [ 136 ]. Figure 4 presents a simplified diagram of the reactional steps that need to be conducted in order to produce new ADCs with homogeneous DARs through engineered amino acid approaches. While enzymatic and linker-based conjugation strategies are increasingly prominent in industrial pipelines, site-specific conjugation techniques with engineered cysteine and non-natural amino acid are presented here as representative models due to their conceptual clarity.

Given the success of ADCs, researchers have already proposed expanding their therapeutic applications [ 6 ]. While most ADCs are in clinical trials for other stages and cancer types, a few ADC candidates are also being explored for non-oncological conditions such as inflammatory diseases and infectious diseases (especially, against Staphylococcus aureus infectious) [ 140 ]. Although not yet in clinical trials, the use of ADCs in neurodegenerative diseases has also been proposed and is under development [ 141 ]. Notwithstanding the fact that all the non-oncological clinical trials form only around 1% of the currently running clinical trials involving ADCs, the potential use of this type of targeted therapy in the future for some diseases beyond cancer is bound to mark one of the biggest advancements in the history of targeted therapies [ 141 ]. Figure 5 illustrates the unique mechanism of action proposed for antibody–antibiotic conjugates, the ADC-derivative approach that uses antibiotics as payloads instead of cytotoxic agents.

5. ADCs in Clinical Trials

Table 3 shows examples of ADCs in phase I–III clinical trials identified in the Clinicaltrials.gov database, indicating targets, payload, condition/disease, and other important observations. Several targets for ADCs are highlighted such as human epidermal growth factor receptor 2 (HER2), trophoblast cell surface antigen 2 (TROP2), human epidermal growth factor receptor 3 (HER3), and claudin 18.2 (CLDN18.2).

6. Conclusions

The history of ADCs is a remarkable example of how precision pharmacotherapy has evolved since the day Paul Ehrlich proposed the concept of “magic bullets”. Although ADCs faced a challenging beginning, they are now believed to have changed the paradigm regarding targeted therapies, a type of treatment that takes advantage of the presence of cell surface receptors to promote the selective delivery of potent cytotoxic agents inside the cytoplasm of cancer cells, while at the same time minimizing unwanted damage to healthy cells.

The introduction of ADCs into the therapeutic drug arsenal available against oncological diseases (hematologic and non-hematologic) has led to significant improvements in the treatment of some types of cancer, specifically in advanced or metastatic stages. However, their clinical use still faces some limitations and challenges that need to be overcome to optimize their therapeutic potential. Several improvements to the target selection and the characteristics of ADC components have been proposed; however, further investigation is still needed. The overall great success achieved with the introduction of ADCs into the drug market has sparked significant interest regarding the expansion of their therapeutic applications to new diseases beyond cancer, such as inflammatory, infectious, and neurodegenerative diseases.

Abbreviations

The following abbreviations are used in this manuscript:

Author Contributions

Conceptualization, A.A., M.L.S.C. and J.C.; methodology, A.A., M.L.S.C. and J.C.; software, A.A., M.L.S.C. and J.C.; validation, M.L.S.C. and J.C.; formal analysis, M.L.S.C. and J.C.; investigation, A.A., M.L.S.C. and J.C.; resources, A.A., M.L.S.C. and J.C.; data curation, M.L.S.C. and J.C.; writing—original draft preparation, A.A.; writing—review and editing, M.L.S.C. and J.C.; visualization, A.A., M.L.S.C. and J.C.; supervision, M.L.S.C. and J.C.; project administration, A.A., M.L.S.C. and J.C. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Conflicts of Interest

The authors declare no conflicts of interest.

Funding Statement

This research received no external funding.

Footnotes

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Associated Data

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.