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Nanobodies for Medical Imaging: About Ready for Prime Time?

Recent advances in medical treatments have been revolutionary in shaping the management and treatment landscape of patients, notably cancer patients. Over the last decade, patients with diverse forms of locally advanced or metastatic cancer, such as melanoma, lung cancers, and many blood-borne malignancies, have seen their life expectancies increasing significantly. Notwithstanding these encouraging results, the present-day struggle with these treatments concerns patients who remain largely unresponsive, as well as those who experience severely toxic side effects. Gaining deeper insight into t

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… For this particular study, the 177 Lu-labeled nanobody was developed as an alternative radioimmunotherapy treatment of HER2-positive breast cancers, as some cancers showed signs of resistance towards traditional anti-HER2 monoclonal antibodies such as Trastuzumab. … The study’s measurements yielded an impressive tumor-to-background ratio and did not exhibit specific binding in the HER2-negative model, indicating the nanobody’s potential as both a radioimmunotherapy and imaging agent for HER2-positive breast cancers [ 55 ]. …

A SWOT-Consensus for CAR-T in Follicular Lymphoma: Fine Tuning of Patient Journey and Selection.

Over the past 2 decades, advancements in follicular lymphoma (FL) treatment, particularly with anti-CD20 antibodies, have significantly improved patient survival. However, a subset of FL patients experiences early relapse and progression within 24 months (POD24) after first line treatment, which is a sign of poor prognosis. Current guidelines recommend various second-line treatments, but there is no consensus on an optimal treatment sequence for relapsed/refractory (r/r) FL. Moreover, despite available treatments, reduced survival after second-line therapies and diminishing responses with each

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… While early ASCT can improve 5‐year OS [ 24 ], the FLAZ12 study reported no significant survival advantage compared to radioimmunotherapy and found higher toxicity in the ASCT arm [ 25 ]. Third‐line treatment strategies typically involve novel therapies or drug combinations not previously used. … Ladetto M., Tavarozzi R., Zanni M., et al., “Radioimmunotherapy versus Autologous Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Follicular Lymphoma: A Fondazione Italiana Linfomi Multicenter, Randomized, Phase III Trial,” Annals of Oncology 35, no. 1 (January 2024): 118–129: Epub 2023 …

A comprehensive prognostic score for head and neck squamous cancer driver genes and phenotype traits.

BackgroundHead and neck squamous cancer (HNSCC) presents variable phenotype and progression features. Clinically applicable, high-accuracy multifactorial prognostic models for HNSCC survival outcomes are warranted and an active area of research. This study aimed to construct a comprehensive prognostic tool for HNSCC overall survival by integrating cancer driver genes with tumor clinical and phenotype information.MethodsKey overall survival-related cancer driver genes were screened from among main effector and reciprocal gene pairs using TCGA data using univariate Cox proportional hazard regres

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… The release of FMS-like tyrosine kinase 3 ligand or FLT3L by natural killer cells is found to enhance HNSCC response to radioimmunotherapy [ 40 ]. Its related protein, CC chemokine receptor 7 (CCR7), has been associated with worse survival in HNSCC [ 41 ]. … FLT3L release by natural killer cells enhances response to radioimmunotherapy in preclinical models of HNSCC. Clin Cancer Res. 2021;27(22):6235–6249. doi: 10.1158/1078-0432.CCR-21-0971. 41. Elmakaty I, Elsayed B, Elmarasi M, Kujan O, Malki MI. …

Management of Patients With Hematologic Malignancies During the COVID-19 Pandemic: Practical Considerations and Lessons to Be Learned.

The COVID-19 pandemic has created unprecedented hurdles to the delivery of care to patients with cancer. Patients with hematologic malignancies appear to have a greater risk of SARS-CoV-2 infection and severe disease due to myelosuppression and lymphopenia. The first challenge, therefore, is how to continue to deliver effective, curative therapy to vulnerable patients and at the same time avoid exposing them, and their health care teams (HCT), to SARS-CoV-2. An additional challenge is the timely completion of the diagnostic and staging studies required to formulate appropriate treatment plans.

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… While radioimmunotherapy remains an underutilized treatment option for relapsed and refractory FL, it has the advantage of requiring only a short course of therapy, with high efficacy and should be considered in selected patients. … The only available radioimmunotherapy agent at this time is ibritumomab tiuxetan (Zevalin). …

The Mode-of-Action of Targeted Alpha Therapy Radium-223 as an Enabler for Novel Combinations to Treat Patients with Bone Metastasis.

Bone metastasis is a common clinical complication in several cancer types, and it causes a severe reduction in quality of life as well as lowering survival time. Bone metastases proceed through a vicious self-reinforcing cycle that can be osteolytic or osteoblastic in nature. The vicious cycle is characterized by cancer cells residing in bone releasing signal molecules that promote the differentiation of osteoclasts and osteoblasts either directly or indirectly. The increased activity of osteoclasts and osteoblasts then increases bone turnover, which releases growth factors that benefit metast

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… Clinical radioimmunotherapy--the role of radiobiology Nat. Rev. Clin. Oncol. 2011 8 720 734 10.1038/nrclinonc.2011.160 22064461 75. Baczyk M. Radioisotope therapy of bone metastases Nucl. Med. Rev. 2011 14 96 104 10.5603/NMR.2011.00023 22219150 76. Kassis A.I. Adelstein S.J. … Immune mechanisms mediating abscopal effects in radioimmunotherapy Pharmacol. Ther. 2019 196 195 203 10.1016/j.pharmthera.2018.12.002 30529041 …

Brain intratumoural astatine-211 radiotherapy targeting syndecan-1 leads to durable glioblastoma remission and immune memory in female mice.

BackgroundGlioblastoma (GB), the most aggressive brain cancer, remains a critical clinical challenge due to its resistance to conventional treatments. Here, we introduce a locoregional targeted-α-therapy (TAT) with the rat monoclonal antibody 9E7.4 targeting murine syndecan-1 (SDC1) coupled to the α-emitter radionuclide astatine-211 (211At-9E7.4).MethodsWe orthotopically transplanted 50,000 GL261 cells of murine GB into the right striatum of syngeneic female C57BL/6JRj mice using stereotaxis. After MRI validation of tumour presence at day 11, TAT was injected at the same coordinates. Biodistri

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… Radioimmunotherapy of neoplastic meningitis in rats using an alpha-particle-emitting immunoconjugate Cancer Res 54 1994 4719 4725 8062270 14 Bäck T. Chouin N. Lindegren S. … Alpha radionuclide-chelated radioimmunotherapy promoters enable local radiotherapy/chemodynamic therapy to discourage cancer progression Biomater Res 26 2022 1 15 36076298 10.1186/s40824-022-00290-6 PMC9461185 64 Brown C.E. Alizadeh D. Starr R. …

Design and Preclinical Validation of an Anti-B7-H3-Specific Radiotracer: A Non-Invasive Imaging Tool to Guide B7-H3-Targeted Therapies.

Background: B7-H3, an immunoregulatory protein of the B7 family, has been associated with both anti-cancer immunity and tumor promotion, with its expression commonly correlated with poor prognosis. Although it is frequently expressed across cancers, its heterogeneity may limit the effectiveness of B7-H3-targeted therapies. Consequently, a sensitive and non-invasive method is needed to assess B7-H3 expression for patient selection and stratification. Single-domain antibody fragments (sdAbs) offer a promising platform for developing such a diagnostic tool. Methods: To generate B7-H3 sdAbs, two I

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… B7-H3-targeted Radioimmunotherapy of Human Cancer Curr. Med. Chem. 2019 27 4016 4038 10.2174/0929867326666190228120908 PMC8668195 30836909 15. Michelakos T. Kontos F. Barakat O. Maggs L. Schwab J.H. Ferrone C.R. Ferrone S. B7-H3 targeted antibody-based immunotherapy of malignant diseases Expert. … Imaging and radioimmunotherapy of multiple myeloma with anti-idiotypic Nanobodies Leukemia 2014 28 444 447 24166214 10.1038/leu.2013.292 31. Li D. Wang R. Liang T. Ren H. Park C. Tai C.H. Ni W. Zhou J. Mackay S. Edmondson E. …

Update on treatment of follicular non-Hodgkin's lymphoma: focus on potential of bortezomib.

Follicular lymphoma is predominantly managed as a chronic disease, with intermittent chemo/immunotherapy reserved for symptomatic progression. It is considered incurable with conventional treatments, and current therapeutic options are associated with significant toxicities that are especially limiting in older patients. Bortezomib (PS-341; Velcade(®)), a first-in-class drug targeting the proteolytic core subunit of the 26S proteasome, has emerged as a therapeutic alternative in follicular lymphoma, with promising preclinical data and efficacy in patients with other hematological malignancies.

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… When patients relapse, treatment options include observation for asymptomatic patients, immunotherapy alone (ie, rituximab), immunotherapy with combination chemotherapy, radioimmunotherapy (conjugate antibody with radioisotope), or, rarely, autologous or allogeneic hematopoietic cell transplantation. … Other potential toxicities may arise if bortezomib is combined with alternative treatment modalities, such as radioimmunotherapy 67 or with important intracellular targets for follicular lymphoma currently in development, such as NF-κB inhibitors, histone deacetylase inhibitors, heat-shock protein 90 …

Rethinking the Combination of Proton Exchanger Inhibitors in Cancer Therapy.

Microenvironmental acidity is becoming a key target for the new age of cancer treatment. In fact, while cancer is characterized by genetic heterogeneity, extracellular acidity is a common phenotype of almost all cancers. To survive and proliferate under acidic conditions, tumor cells up-regulate proton exchangers and transporters (mainly V-ATPase, Na⁺/H⁺ exchanger (NHE), monocarboxylate transporters (MCTs), and carbonic anhydrases (CAs)), that actively extrude excess protons, avoiding intracellular accumulation of toxic molecules, thus becoming a sort of survival option with many similarities

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… Lastly, radioimmunotherapy with Lutetium 177–labeled girentuximab are also well tolerated in metastatic ccRCC patients [ 170 ]. 5. … Phase 1 radioimmunotherapy study with lutetium 177-labeled anti-carbonic anhydrase IX monoclonal antibody girentuximab in patients with advanced renal cell carcinoma Eur. Urol. 2013 64 478 485 10.1016/j.eururo.2012.08.024 22980441 171. Lugini L. Sciamanna I. Federici C. Iessi E. Spugnini E.P. …

Keyword Index for Volume 108

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… 2153 quality of care 1942 quality of life 301, 1225, 1571, 1790 quaternary cytoreduction 32 radiation 91, 1106, 1225 radiation-induced neoplasm 1579 radiation-related heart disease 179 radiation-related lung cancer 179 radiation therapy 1964 radical hysterectomy 1348 radical surgery 1957 radioimmunotherapy …

Consensus recommendations from the 2024 International Follicular Lymphoma Scientific Workshop.

AbstractFollicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. Although patients with FL have high response rates to therapy, most develop increasingly resistant disease. In addition, transformation into an aggressive lymphoma is associated with unfavorable outcomes. Many novel agents are under investigation, and early clinical data are encouraging. Aligning treatment with the underlying tumor biology and sequencing of therapies remain key clinical challenges. At the Lymphoma Research Foundation's biannual 2024 Follicular Lymphoma Scientific Workshop, experts convened to di

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… There are numerous examples of treatments that improve PFS but are used selectively or not at all because of toxicity concerns (radioimmunotherapy, ASCT, obinutuzumab, and CD20 mAb maintenance). 8 , 37 , 46 , 84 , 96 Safety and tolerability are critical considerations in a disease in which patients have … survival is a weakly predictive surrogate end-point for overall survival in follicular lymphoma: a systematic review and meta-analysis Br J Haematol 204 6 2024 2237 2241 38571449 10.1111/bjh.19449 96 Witzig TE Gordon LI Cabanillas F Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy …

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lymphoma.

The recent development and clinical implementation of novel immunotherapies for the treatment of Hodgkin and non-Hodgkin lymphoma have improved patient outcomes across subgroups. The rapid introduction of immunotherapeutic agents into the clinic, however, has presented significant questions regarding optimal treatment scheduling around existing chemotherapy/radiation options, as well as a need for improved understanding of how to properly manage patients and recognize toxicities. To address these challenges, the Society for Immunotherapy of Cancer (SITC) convened a panel of experts in lymphoma

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… placebo+rituximab-chemotherapy for R/R indolent NHL | mAb and PI3Ki | Rate of dose-limiting toxicities/AEs, PFS UNITY-NHL ( NCT02793583 ) | TGR-1202+ublituximab vs TGR-1202 vs TGR-1202+ublituximab+bendamustine for R/R NHL | mAb and PI3Ki | ORR NCT02320292 | Rituximab+IT vs rituximab for first-line FL | Radioimmunotherapy …

New insights into non-small cell lung cancer bone metastasis: mechanisms and therapies.

Bone metastasis is a common cause of death in patients with non-small cell lung cancer (NSCLC), with approximately 30-40% of NSCLC patients eventually developing bone metastases. Bone metastasis, especially the occurrence of skeletal-related events (SREs), significantly reduces overall survival (OS) and quality of life (QoL) in patients. Although bone-targeting agents (BTAs) have been shown to reduce SREs and improve QoL in NSCLC patients with bone metastases, the prognosis for these patients remains poor. Understanding the underlying molecular pathways of bone metastasis is crucial for the de

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… Furthermore, radioimmunotherapy shows advantages in clinical treatment of cancer and metastasis. … Dirix P Stereotactic Body and Conventional Radiotherapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis JAMA Netw Open 2024 7 e2355409 38345820 10.1001/jamanetworkopen.2023.55409 PMC10862159 106 Ashrafizadeh M Farhood B Eleojo Musa A Taeb S Rezaeyan A Najafi M Abscopal effect in radioimmunotherapy …

Promising Therapeutic Strategies for Hematologic Malignancies: Innovations and Potential.

In this review we explore innovative approaches in the treatment of hematologic cancers by combining various therapeutic modalities. We discuss the synergistic potential of combining inhibitors targeting different cellular pathways with immunotherapies, molecular therapies, and hormonal therapies. Examples include combining PI3K inhibitors with proteasome inhibitors, NF-κB inhibitors with immunotherapy checkpoint inhibitors, and neddylation inhibitors with therapies targeting the tumor microenvironment. Additionally, we discuss the potential use of small molecules and peptide inhibitors in hem

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… Radioimmunotherapy, which integrates radiotherapy with immunotherapy by using radioactive substances attached to antibodies, specifically targets cancer cells. … Potentially Toxic Therapies Three of the most potentially toxic therapies in cancer treatment are radioimmunotherapy, gene therapy, and hyperthermic therapy. …

A Rare Presentation of Multiple Myeloma as a Second Primary Cancer Sequential to Non-Hodgkin Lymphoma: Case Report.

INTRODUCTION: The sequential occurrence of diffuse large B-cell lymphoma (DLBCL) a common type of non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) is exceedingly rare, presenting a significant challenge in both diagnosis and treatment. CASE PRESENTATION: The case report discusses a 60-year-old male patient with a history of DLBCL which was diagnosed following symptoms of fever, weight loss and night sweats. He was treated with RVP (rituximab 375 mg/m2, vincristine 1.4 mg/m2, prednisolone 60 mg/m2) and R-CHOP regimen (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2,

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… In addition, procedures such as splenectomy and therapies such as rituximab or radioimmunotherapy with zevalin (ibritumomab tiuxetan) have also been significantly associated with an increased risk of developing MM as a SPM [ 3 ]. …

A brief overview of targeted radionuclide therapy trials in 2022.

There is a growing use of radionuclide therapy for the medical care of oncology patients, where radioactive pharmaceuticals are used to target and treat various cancer types. This paper provides a brief overview illustrating the spectrum of ongoing and recently completed radionuclide therapy clinical trials in oncology. The trials selected highlight the potential of radionuclide therapies to provide a promising treatment option across a spectrum of cancer patients, while also discussing the importance of patient selection and monitoring, as well as potential side effects and safety concerns. U

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… Radioimmunotherapy (RIT) is a type of targeted therapy that involves using a radioactive isotope conjugated to a monoclonal antibody (mAb) to selectively deliver radiation and immunotherapy to cancer cells expressing the targeted protein. …

Monoclonal Antibodies Against Myeloid Leukemia Cells: Current Knowledge and Future Directions.

Monoclonal antibodies targeting specific cell surface antigens have emerged as a promising therapeutic approach for acute myeloid leukemia (AML), thus widening the treatment landscape of this heinous disease. These antibodies have been designed to selectively target and eliminate leukemic cells while limiting damage to the normal hematopoietic counterpart. Among the potential targets on AML cells, CD33, CD123, and CD47 have shown the major potential in preclinical and clinical trials. Additionally, conjugation of monoclonal antibodies with cytotoxic agents has further enhanced their therapeuti

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… Radio-Conjugated Antibodies Radioimmunotherapy (RIT) utilizes MAbs labeled with radio nuclides, assuring continuous radiation exposure to cells expressing target antigens. RIT can deliver ionizing radiation to disease sites more specifically than traditional total body irradiation. … Anti-cd45 radioimmunotherapy without tbi before transplantation facilitates persistent haploidentical donor engraftment. Blood. 2016;127:352–359. doi: 10.1182/blood-2014-12-617019. 143. …

Defining neuroblastoma: From origin to precision medicine.

Neuroblastoma (NB), a heterogenous pediatric tumor of the sympathetic nervous system, is the most common and deadly extracranial solid malignancy diagnosed in infants. Numerous efforts have been invested in understanding its origin and in development of novel curative targeted therapies. Here, we summarize the recent advances in the identification of the cell of origin and the genetic alterations occurring during development that contribute to NB. We discuss current treatment regimens, present and future directions for the identification of novel therapeutic metabolic targets, differentiation

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… The available immunotherapies for NB treatment include immune checkpoint inhibitors such as anti-CTLA-4, anti-PD-1/PDL-1, anti-GD2 and anti-B7-H3 mAbs, and adoptive NK cells, radioimmunotherapy with B7-H3 mAbs, anti-GD2 vaccine, PC-CARs, and CAR-T cells. … A clinical study using compartmental radioimmunotherapy (cRIT) with the anti-B7H3 murine monoclonal antibody omburtamab showed both safety and therapeutic efficacy in metastatic NB. 146 Bispecific antibodies are being developed, including anti-GD2 anti-B7-H3 antibodies. …

Radiotherapy and cytokines: A systems view of immunotherapy and toxicity (Review).

Radiotherapy (RT) is increasingly recognized as a system‑level immunomodulator capable of reshaping cytokine networks across spatial, temporal and dosimetric dimensions. This review synthesizes existing evidence on RT parameters, key signaling axes, major effector cells, organ‑specific contexts and clinical translation. It describes how the cyclic GMP‑AMP synthase/stimulator of interferon genes (STING)/IFN‑I, NF‑κB and TGF‑β pathways coordinate immune activation and immune suppression after irradiation. It then summarizes macrophage‑centered regulatory circuits and chemokine axes, including C‑

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… Ionizing radiation can influence therapeutic success by initiating immune signaling cascades, positioning RT as a core component of radioimmunotherapy ( 61 ). Different RT modalities can regulate cytokine programs in distinct ways. … With improved mechanistic resolution and clinically implementable monitoring and intervention strategies, RT can be developed as a component of systemic immunomodulatory treatment, supporting individualized radioimmunotherapy. Acknowledgements Not applicable. …

Meeting abstracts from the 21st European Symposium on Radiopharmacy and Radiopharmaceuticals

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