Research Topic

Bispecific Antibodies for T-Cell Based Immunotherapy

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In recent years, immunotherapy has brought significant improvements to cancer treatment. Among many directions immunotherapy research has taken in oncology, several therapeutics have had enough clinical success to garner government approval, including T-cell bispecific antibodies (BsAb) blinatumomab and ...

In recent years, immunotherapy has brought significant improvements to cancer treatment. Among many directions immunotherapy research has taken in oncology, several therapeutics have had enough clinical success to garner government approval, including T-cell bispecific antibodies (BsAb) blinatumomab and catumaxomab. T-cell bispecific antibodies possess several key properties that drive their preclinical and clinical success as an immunotherapy platform: engagement of T-cells, exquisite antigen specificity, high level of modularity as well as the relative ease of drug distribution and administration.

T-cells remain the most well-studied cell type for cancer immunotherapy, across a broad spectrum of platforms (e.g. BsAb, immune checkpoint inhibitors, CAR-T), targets and tumor types. In contrast to small molecules or chemotherapy that often bind multiple targets and lead to off-target toxicities, the specificity of bispecific antibodies is only limited by the underlying target expression profile. Furthermore, the number of ways in which bispecific antibodies can be engineered in nearly limitless: valency, size, affinity, and flexibility can all be easily optimized to best fit the indication. Finally, unlike cell therapies or gene therapies, bispecific antibodies are dispensed as conventional pharmaceuticals making them easily accessible in both hospital and private practice settings. Despite the above-mentioned advantages, the progress in T-cell bispecific antibody research has been somewhat slow, especially in the realm of solid tumors, which are responsible for the majority (>90%) of cancer deaths worldwide. This could be in part due to suboptimal tumor antigens leading to dose-limiting toxicities and overactivation of the immune system (cytokine release syndrome) as well as insufficient drug potency because of the inhibitory tumor microenvironments.

In this Research Topic, we would like to focus on the development, clinical application, current limitations, and future directions of T-cell bispecific antibodies. Topics may include, but are not limited to:

1) Novel T-cell bispecific antibody targets and designs
2) Evaluation of safety, biomarkers or prognostic indicators for bispecific antibody therapy
3) Clinical responses to T-cell bispecific antibodies monotherapy and combination therapies
4) T-cell immunology in the context of bispecific antibody therapy

We welcome both Original Research and Review articles.

CK is affiliated with the Roche Innovation Center Zurich, holds stocks and has patents with Hoffmann-La Roche company. NKC reports receiving commercial research grants from Y-mabs Therapeutics and Abpro-Labs Inc.; holding ownership interest/equity/options in Y-Mabs Therapeutics Inc., and in Abpro-Labs, and owning stock options in Eureka Therapeutics. NKC is the inventor of pending and issued patents filed by MSK, including hu3F8 and 8H9 licensed to Ymabs Therapeutics, beta-glucan to Biotec Pharmacon, and HER2 bispecific antibody to Abpro-labs. NKC is an advisory board member for Abpro-Labs and Eureka Therapeutics


Keywords: Bispecific antibody, T-cells, immunotherapy, immunooncology, cancer, protein therapy


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