Bi-specific and tri-specific antibodies- the next big thing in solid tumor therapeutics

Abstract

Antibody-based therapy has revitalized the world of cancer therapeutics since rituximab was first approved for the treatment of Non-Hodgkin’s Lymphoma. Monoclonal antibodies against cancer antigens have been successful strategies for only a handful of cancer types due to many reasons including lack of antibody specificity and complex nature of tumor milieu which interfere with antibody efficacy. Polyspecific antibodies are promising class of anti-cancer agents which can be directed at multiple tumor antigens to eradicate tumor cells more precisely and effectively. They may overcome some of these limitations and have already changed treatment landscape for some malignancies such as B cell acute lymphoblastic leukemia. Pre-clinical studies and early phase clinical trials have demonstrated that this approach may be an effective strategy even for solid tumors. This review focuses on the development of bispecific and trispecific antibody therapy for the treatment of solid tumor malignancies and highlights the potential they hold for future therapies to come.

Unleashing Natural Killer Cells in the Tumor Microenvironment–The Next Generation of Immunotherapy?

“…The challenges facing therapy involving NK cell engagers include the complexity of the design process, screening, production yield, and selection of the proper tumor antigen (277). Often, tumor antigens are expressed on otherwise healthy tissue, adding an obstacle to possible on-target/off-tumor toxicity, requiring proper screening prior to development (17).…”

Single cell-produced and in vitro-assembled anti-FcRH5/CD3 T-cell dependent bispecific antibodies have similar in vitro and in vivo properties

“…[5][6][7] There is also growing interest on developing bispecifics and T-cell recruiting therapeutics for solid tumors. [8][9][10] Previously, we described the design, mechanism of action (MOA) and pharmacokinetics (PK)/pharmacodynamics (PD) of an in vitro-assembled anti-FcRH5/CD3 TDB. 11 The anti-CD 3 arm of this T-cell dependent bispecific (TDB) engages T cells and the anti-FcRH5 arm engages FcRH5-expressing cells such as B cells, PCs and MM cells to form an immunological synapse.…”

Synthesis and evaluation of designed PKC modulators for enhanced cancer immunotherapy

“…T argeted biologics and cell therapies for the treatment of cancer, including monoclonal antibodies (mAbs) 1 , antibodydrug conjugates (ADC's) 2 , bi-and tri-specific antibodies (biAbs, triAbs) 3 , chimeric antigen receptor (CAR) T and NK cell therapies, and neoantigen-directed cell therapies [4][5][6] , are revolutionizing oncology. By targeting tumor-specific cell surface antigens and neoantigens, these therapies offer distinct advantages over traditional treatment options as they avoid the systemic toxicity associated with cytotoxic chemotherapies while efficiently and selectively clearing malignant cells 7,8 .…”