Research

Life Sciences & Biotechnology

Title :

Harnessing efficiency of spontaneous anti-tumor humoral responses and antibody-based immunotherapies in epithelial malignancies

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. Gunjan Mandal, Institute Of Life Sciences (ILS), Bhubaneswar, Odisha

Timeline Start Year :

2024

Timeline End Year :

2026

Contact info :

Details

Executive Summary :

The field of tumor immunology has traditionally focused on T cell-mediated humoral immune responses, but recent evidence supports that humoral responses by tumor-infiltrating B-cells (TIL-B cells) are associated with immune protection in multiple human solid tumors. IgA is the most dominant class of immunoglobulin in human endometrial and ovarian cancer, and IgG antibodies are also observed to be spontaneously produced in both gynecological cancer types studied. However, in many cancers, such as breast cancer, IgG antibodies are the predominant class of immunoglobulin produced at tumor beds. A foundational study is proposed to understand how primary cancer tissues bypass the anti-tumor functions of the spontaneous IgG antibodies produced naturally by TIL-B cells at tumor beds. The central hypothesis is that Neonatal Fc Receptor (FcRn) sequesters IgG antibodies and abrogates the anti-tumor functions of IgG antibodies produced by tumor infiltrating plasma cell B lymphocytes. This hypothesis is based on preliminary observations that Neonatal Fc Receptor is expressed quasi-universally by most epithelial cancer tissues and many non-epithelial cancers. Experiments using clinical specimens, in vivo models, and in vitro settings will uncover the role of expression of FcRn by cancer cells and provide insights into future therapeutic targets applicable to multiple cancer types.

Total Budget (INR):

30,70,480

Organizations involved