XII. Therapeutic exploitation of autologous T‐cell activation in B‐cell lymphoma

T lymphocytes play a critical role in the immune defense against foreign pathogens and cancer. For the past few decades, activating autologous T cells was primarily achieved through vaccination and cytokine stimulation. For native T cells to be activated, T-cell receptors must recognize a peptide that is presented by an antigen-presenting cell through Human Leukocyte Antigen (HLA) classes I and II. In contrast, antibodies, including surface-bound B-cell receptors, can recognize surface antigens independent of HLA restriction. Most antibodies induce anti-tumour response through antibody-dependent cytotoxicity and complement-dependent cytotoxicity. Because most tumour cells are either poor antigen presenters or frequently develop mechanisms to evade immune-cell recognition, investigators developed molecular methods to induce T-cell activation by cell surface proteins, rather than through HLA-restricted peptides. By doing so, a large pool of T cells can be activated by a variety of tumour antigens. Onemethod is to engineer bispecific antibodies that bind to a target antigen on tumour cells, and CD3 on T lymphocytes. Initially, bispecific antibodies consisted of two full antibodies fused at their Fc tails. More recently, smaller molecules were generated to better facilitate tumour site penetration. This review will focus on recent data on the use of engineered chimeric antigen receptor (CAR) T cells and immune checkpoint inhibitors in lymphoma (Figure 1).