CAR T-Cell-Based Combination Therapy for Pancreatic Ductal Adenocarcinoma (PDAC)

Abstract

It is projected that by 2030, following the lung cancer, pancreatic cancer will rank among the deadliest cancers. Because of the limited initial symptoms and early diagnosis, PDAC has one of the most dismal prognosis among all types of malignancies. Therefore, it is crucial to develop promising treatments for PDAC cases. Genetically engineering the T lymphocytes to express designed chimeric antigen receptors (CAR) is an emerging direction, but the major hindrance is the complex tumor microenvironment (TME) that restricts its performance. This review paper discusses the existing combinations between CAR T-cell and other therapies, the challenges, and future improvements in promoting the therapeutic outcomes of PDAC. Multiple chemotherapeutic drugs remodel the complicated TME to upregulate the potency of T cells. Some radiotherapies augment tumor-associated antigen expression to increase the anticancer activities. Additionally, the cytotoxicity of the engineered T cells is enhanced by checkpoint inhibitor blockade (CPB). Oncolytic viruses (OVs) represent another novel approach in CAR T-cell combination. OVs stimulate cytokines, which then trigger the chemokines in CAR-T-cell regulations. Being well-versed in the potential concurrent therapies in CAR T-cell-based manner facilitates researchers in conducting future studies in a more targeted way towards PDAC.