The recent advances in the field of immuno-oncology have dramatically changed the therapeutic strategy against advanced malignancies. Bispecific antibody-based immunotherapies have gained momentum in preclinical and clinical investigations following the regulatory approval of the T cell-redirecting antibody blinatumomab. In this review, we focus on emerging and novel mechanisms of action of bispecific antibodies interacting with immune cells with at least one of their arms to regulate the activity of the immune system by redirecting and/or reactivating effector cells toward tumor cells. These molecules, here referred to as bispecific immunomodulatory antibodies, have the potential to improve clinical efficacy and safety profile and are envisioned as a second wave of cancer immunotherapies. Currently, there are more than 50 bispecific antibodies under clinical development for a range of indications, with promising signs of therapeutic activity. We also discuss two approaches for secretion, direct gene delivery, and infusion of gene-modified cells, which may become instrumental for the clinical application of next-generation bispecific immunomodulatory antibodies.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306338 | PMC |
http://dx.doi.org/10.1158/1078-0432.CCR-20-3770 | DOI Listing |
J Immunother Cancer
January 2025
Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan
Background: A number of immunotherapeutic approaches have been developed and are entering the clinic. Bispecific antibodies (BsAbs) are one of these modalities and induce robust efficacy by endogenous T cells in several hematological malignancies. However, most of the treated patients experience only a temporary benefit.
View Article and Find Full Text PDFSignal Transduct Target Ther
January 2025
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Immunomodulatory agent lenalidomide is effective in treating follicular lymphoma (FL). We conducted the first trial of immunotherapy rituximab plus lenalidomide in newly diagnosed FL in China (NCT03715309). One-hundred and fifteen patients were enrolled and treated with rituximab 375 mg/m intravenously on day 0 and lenalidomide 25 mg orally on day 1-10 for 6 cycles of induction treatment, as well as lenalidomide for 6 cycles and rituximab for 8 cycles of maintenance treatment.
View Article and Find Full Text PDFClin Lymphoma Myeloma Leuk
November 2024
Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany. Electronic address:
Despite significant advancements, multiple myeloma (MM) remains incurable, and there is still a pressing need for new therapeutic strategies with highly selective mechanisms of action and balanced off-target toxicity. In recent years, the development of "off-the-shelf" bispecific antibodies (bsAbs) has significantly enhanced our ability to treat relapsed or refractory MM. Teclistamab, elranatamab (both BCMA × CD3), and talquetamab (GPRC5D × CD3) are approved for treating MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.
View Article and Find Full Text PDFPresse Med
December 2024
Sorbonne Université, Centre de Recherche Saint-Antoine INSERM UMRs938, Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France. Electronic address:
Minimal Residual Disease (MRD) in multiple myeloma has emerged as a significant prognostic factor, guiding treatment strategies and enhancing patient outcomes. Despite advancements in therapies such as proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, CAR-T cell therapy, and bispecific antibodies, complete eradication of malignant plasma cells remains challenging. MRD refers to a small number of residual cancer cells that persist after treatment and require sensitive methods like next-generation flow cytometry (NGF) and next-generation sequencing (NGS) for detection.
View Article and Find Full Text PDFPresse Med
December 2024
Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany. Electronic address:
Although the prognosis of patients with multiple myeloma (MM) has been significantly improved by the introduction of proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies, MM is still considered an incurable disease in the vast majority of the patients. In recent years, T-cell based immunotherapy represents a novel treatment strategy for relapsed/refractory (RR) MM. So far, chimeric antigen receptor (CAR) modified T-cells and bispecific T-cell engaging antibodies (bsAb) have shown promising anti-MM efficacy and manageable safety profile within clinical trials, and B-cell maturation antigen (BCMA) is the most commonly used immune target for T-cell based immunotherapies in MM.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!