Cellular therapy approaches harnessing the power of the immune system for personalized cancer treatment

Abstract

Cancer development often implies failure of the immune system to recognize tumor antigens and kill malignant cells. While the whole immune cell repertoire is broad, that of immune cells with the ability to react to individual tumor antigens is usually very limited. The purpose of cancer immunotherapy is to augment the power, quantitative and qualitative, of the immune system such that it readily recognizes and eliminates cancer cells. As immune therapy is shifting toward more personalized medicine, different types of tumor antigens can be used as target antigens to allow T cells to destroy tumor cells. These antigens are mostly defined as tumor associated antigens (TAA), neoantigens or minor histocompatibility antigens. Their clinical usage involve either direct injection of TAA and neoantigens, administration of peptide-loaded dendritic cells in vaccination approaches, or infusion of ex vivo expanded tumor-specific T cells. However, such cellular therapies are facing several challenges including immune suppressive tumor microenvironment, lack of persistence of ex vivo expanded antigen specific T cells and potential off-target toxicity of these therapies. In this review, we will discuss recent advances allowing for better expansion of tumor reactive T cells and novel strategies used to overcome the challenges facing cellular therapy for cancer.

Keywords: Adoptive cell therapy; Cancer immunotherapy; Checkpoint blockade; Dendritic cell; Minor histocompatibility antigen; T lymphocyte; Tumor associated antigen.