T-Cell Receptor-Based Immunotherapy for Hematologic Malignancies

Adoptive immunotherapy with engineered T cells is at the forefront of cancer treatment. T cells can be engineered to express T-cell receptors (TCRs) specific for tumor-associated antigens (TAAs) derived from intracellular or cell surface proteins. T cells engineered with TCRs (TCR-T) allow for targeting diverse types of TAAs, including proteins overexpressed in malignant cells, those with lineage-restricted expression, cancer-testis antigens, and neoantigens created from abnormal, malignancy-restricted proteins. Minor histocompatibility antigens can also serve as TAAs for TCR-T to treat relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation. Moreover, TCR constructs can be modified to improve safety and enhance function and persistence of TCR-T. Transgenic T-cell receptor therapies targeting 3 different TAAs are in early-phase clinical trials for treatment of hematologic malignancies. Preclinical studies of TCR-T specific for many other TAAs are underway and offer great promise as safe and effective therapies for a wide range of cancers.