Discovering the Biochemical Properties and Antigen Targets of Tumour-Infiltrating B Lymphocyte Antibodies

Abstract

Immunotherapies using T cells have had fantastic success in hematological malignancies or blood cancers, but the treatment has yet to prove effective for solid tumours. To improve the effectiveness of immunotherapies, we need to harness other powerful immune cells, like tumour-infiltrating B cells (TIL-B). Indeed, TIL-B and their antibodies are associated with prolonged patient survival in several cancers, yet their antigen targets and exact mechanisms remain poorly understood. We seek to understand what these antibodies do and what they are binding in the tumour environment. We hypothesize that TIL-B plays a critical role in anti-tumour immunity by producing antibodies that recognize tumour-relevant antigens and mediate various immunological effects. We found that highly reactive antibodies have shorter binding sites than weakly reactive antibodies. As well we found using rAscal (recombinant antibody screening of cDNA antigen library) that a TIL-B antibody binds histone 2 variant 1, a nuclear protein. As we continue to learn more about the antigen targets, we will decipher the role of TIL-B in the anti-tumour response, which will advance the next generation of immunotherapies.