T Lymphocytes with Modified Specificity in the Therapy of Malignant Diseases

Immunotherapy is one of the most rapidly progressing and promising fields in antitumor therapy. It is based on the idea of using immune cells of patient or healthy donors for elimination of malignant cells. T lymphocytes play a key role in cell-mediated immunity including the response to tumors. Recently developed approaches of altering antigen specificity of T cells consist of their genetic modification (introduction of additional T cell receptor or chimeric antigen receptor), as well as the use of bispecific molecules that crosslink target and effector cells. These approaches are used to retarget T lymphocytes with arbitrary specificity against tumor antigens in the context of antitumor immunotherapy. The high potential of T cell immunotherapy was demonstrated in a number of clinical trials. In the future, it is possible to develop approaches to the therapy of a wide spectrum of tumors. The selection of the optimal antigen is the main challenge in successful T cell immunotherapy, as it largely determines the effectiveness of the treatment, as well as the risk of side effects. In this review we discuss potential methods of modification of T cell specificity and targets for immunotherapy.