Adoptive Cell Therapy Targeting Neoantigens: A Frontier for Cancer Research

Abstract

Adoptive cell therapy (ACT) is a kind of immunotherapy in which T cells are genetically modified to express a chimeric antigen receptor (CAR) or T cell receptor (TCR), and ACT has made a great difference in treating multiple types of tumors. ACT is not perfect, and it can be followed by severe side effects, which hampers the application of ACT in clinical trials. One of the most promising methods to minimize side effects is to endow adoptive T cells with the ability to target neoantigens, which are specific to tumor cells. With the development of antigen screening technologies, more methods can be applied to discover neoantigens in cancer cells, such as whole-exome sequencing combined with mass spectrometry, neoantigen screening through an inventory-shared neoantigen peptide library, and neoantigen discovery via trogocytosis. In this review, we focus on the side effects of existing antigens and their solutions, illustrate the strategies of finding neoantigens in CART and TCR-T therapies through methods reported by other researchers, and summarize the clinical behavior of these neoantigens.

PET/CT imaging for tumour response assessment to immunotherapy: current status and future directions

“…The cells are equipped with artificial CARs, which are composed of an antibody-derived single-chain variable fragments, a transmembrane and a signalling domain [16]. The single-chain variable fragment allows recognition of surface bound tumourassociated antigens such as CD19, whereas physiological T cell receptors are restricted to recognition of antigen fragments presented via the major histocompatibility complex [2]. Upon antigen binding, the CAR induces activation, proliferation of and cytokine release by the T cells, followed by cytotoxic activity targeted against the respective cancer cells.…”

“…15, 81377 Munich, Germany. 2 Department of Medicine III, University Hospital, LMU Munich, Munich, Germany. 3 Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany.…”

“…Active immunotherapy uses agents that direct the immune system to attack tumour cells by targeting tumour antigens (e.g., vaccines such as Bacillus Calmette-Guérin in bladder cancer). Active cellular-based therapies are on the rise, most notably chimeric antigen receptor (CAR) T cell therapy, which redirects patientderived T cells against tumour antigens [1][2][3].…”

CAR T Cell Therapy for Solid Tumors: Bright Future or Dark Reality?

“…In addition, most neoantigens described so far are derived from intracellular proteins, which are difficult to target with standard CAR T cells. 137 Investigators have therefore embarked on discovering novel CAR targets using genomic and proteomic approaches. [138][139][140] In addition, there is an intense focus on engineering CARs and CAR T cells to increase their specificity for antigens expressed on tumor cells.…”

Modulation of TCR Signaling by Tyrosine Phosphatases: From Autoimmunity to Immunotherapy

“…TSAs refer to antigens and neoantigens that often newly arise from acquired genetic variants. As these are antigens that the adaptive immune system has not experienced previously, TSAs usually elicit vigorous immune responses that are specific to the cancer cells (Robbins et al, 2013;Lu et al, 2014) and are thought to elicit fewer on-target off-tumor effects in the patient because their expression is restricted to the tumor (Wang and Cao, 2020). TAAs on the other hand include embryonic/differentiation antigens and overexpressed self-antigens.…”