Bispecific antibodies constitute a novel approach to improve antibody efficacy. In vitro, constructs to recruit myeloid effector cells have been extensively investigated, and first animal data in human Fc receptor transgenic mice confirmed their promising therapeutic potential. Clinical experience with these constructs demonstrated acceptable toxicity, and support therapeutic efficacy in subgroups of patients. However, limited availability, unacceptable immunogenicity, and unfavorable pharmacokinetics of bispecific compared to conventional antibodies often hampered clinical studies. As solutions to these problems are available today, bispecific antibodies hold promise to improve therapeutic efficacy of antibody-based approaches in the near future.
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http://dx.doi.org/10.1016/s1040-8428(00)00135-9 | DOI Listing |
MAbs
December 2025
Ichnos Glenmark Innovation, New York, NY, USA.
ISB 1442 is a bispecific biparatopic antibody in clinical development to treat hematological malignancies. It consists of two adjacent anti-CD38 arms targeting non-overlapping epitopes that preferentially drive binding to tumor cells and a low-affinity anti-CD47 arm to enable avidity-induced blocking of proximal CD47 receptors. We previously reported the pharmacology of ISB 1442, designed to reestablish synthetic immunity in CD38+ hematological malignancies.
View Article and Find Full Text PDFSemin Hematol
December 2024
Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:
Recent advancements in multiple myeloma (MM) treatment-including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and T cell-redirecting therapies like chimeric antigen receptor (CAR) T cells and bispecific antibodies (BsAbs)-have significantly improved patient outcomes. However, MM remains incurable, highlighting the need for novel therapeutic strategies. BsAbs, which simultaneously target a tumor-specific antigen and CD3 on T cells, have shown promising efficacy.
View Article and Find Full Text PDFTarget Oncol
January 2025
Berenson Cancer Center, West Hollywood, CA, USA.
Multiple myeloma (MM) is a bone-marrow-based cancer of plasma cells. Over the last 2 decades, marked treatment advances have led to improvements in the overall survival (OS) of patients with this disease. Key developments include the use of chemotherapy, immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies.
View Article and Find Full Text PDFFront Immunol
January 2025
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
The non-polio Enteroviruses (NPEVs), consist of enteroviruses, coxsackieviruses, echoviruses, and rhinoviruses, are causative agents for a wide variety of diseases, ranging from common cold to encephalitis and acute flaccid paralysis (AFP). In recent years, several NPEVs have become serious public health threats, include EV-A71, which has caused epidemics of hand-foot-and-mouth disease (HMFD) in Southeast Asia, and EV-D68, which caused outbreaks of severe respiratory disease in children worldwide. Infections with these viruses are associated with neurological diseases like aseptic meningitis and AFP.
View Article and Find Full Text PDFCancer
February 2025
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center, Baltimore, Maryland, USA.
Tarlatamab is a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 (DLL3) and the cluster of differentiation 3 (CD3) molecule. In the phase 2 DeLLphi-301 trial of tarlatamab for patients with previously treated small cell lung cancer, tarlatamab 10 mg every 2 weeks achieved durable responses and encouraging survival outcomes. Analyses of updated safety data from the DeLLphi-301 trial demonstrated that the most common treatment-emergent adverse events were cytokine release syndrome (53%), pyrexia (38%), decreased appetite (36%), dysgeusia (32%), and an emia (30%).
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