Development of Cloned B Cell Populations as Immunotherapeutic Agents Against Myc Carcinogenic Proteins

Abstract

The MYC proto-oncogene is one of the most extensively dysregulated transcription factors in cancer, governing cell cycle progression, metabolic adaptation, and immune evasion. Despite its central role in tumor biology, MYC has been considered an undruggable target due to its nuclear localization, lack of enzymatic activity, and involvement in transcriptional regulation. The emergence of B-cell based immunotherapies has reshaped the understanding of tumor immunology, revealing that B cells exert both effector and regulatory roles in tumor microenvironment. The intersection between MYC biology and B-cell function is relevant, as MYC is indispensable for B-cell maturation and is frequently dysregulated in B-cell-derived malignancies such as Burkitt lymphoma and diffuse large B-cell lymphoma. We focus specifically on the intersection between MYC-driven oncogenic signaling and emerging B-cell-based immunotherapeutic platforms. This review proposes a conceptual reference framework in which MYC is considered not only as a proliferative driver but also as an immune-modulating oncogene that can aid in the design of humoral therapeutic strategies. Therapeutic strategies to inhibit MYC are systematically discussed, including BET and CDK inhibitors, disruption of MYC–MAX dimerization, RNA-based technologies, synthetic lethality approaches, and emerging PROTACs. Cloned B-cell populations, effector B-cells secreting intrabodies, CAR-B platforms, and antibody-based intracellular targeting are areas of focus. An overview is presented of preclinical and clinical advances made thus far, as well as challenges to the successful translation of these therapies for use in patients including tumor heterogeneity, limitations associated with delivery of agents, and risk of inducing autoimmunity. Forecasting the future provides rationale for combining MYC-targeting agents with immunotherapies and using personalized neoantigen-driven B-cell immunotherapies to treat patients with cancer. Overall, these findings support the concept that MYC B-cell-directed strategies will represent a novel means of treating patients with cancer through their development into new classes of therapeutics.

Keywords: MYC Oncogene, Cancer Immunotherapy,, Antibody Engineering, CAR-B Cells, B Cells in Tumor Microenvironment, Translational Oncology