Yeo Dannel, Giardina Caroline, Saxena Payal, Rasko John E J
Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, NSW 2050, Australia.
Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia.
Mol Ther Oncolytics. 2022 Feb 1;24:561-576. doi: 10.1016/j.omto.2022.01.010. eCollection 2022 Mar 17.
Pancreatic cancer is an aggressive disease that is predicted to become the second leading cause of cancer-related death worldwide by 2030. The overall 5-year survival rate is around 10%. Pancreatic cancer typically presents late with locally advanced or metastatic disease, and there are limited effective treatments available. Cellular immunotherapy, such as chimeric antigen receptor (CAR) T cell therapy, has had significant success in treating hematological malignancies. However, CAR T cell therapy efficacy in pancreatic cancer has been limited. This review provides an overview of current and ongoing CAR T cell clinical studies of pancreatic cancer and the major challenges and strategies to improve CAR T cell efficacy. These strategies include arming CAR T cells; developing off-the-shelf allogeneic CAR T cells; using other immune CAR cells, like natural killer cells and tumor-infiltrating lymphocytes; and combination therapy. Careful incorporation of preclinical models will enhance management of affected individuals, assisting incorporation of cellular immunotherapies. A multifaceted, personalized approach involving cellular immunotherapy treatment is required to improve pancreatic cancer outcomes.
胰腺癌是一种侵袭性疾病，预计到2030年将成为全球癌症相关死亡的第二大主要原因。总体5年生存率约为10%。胰腺癌通常在疾病局部进展或转移时才出现较晚症状，且可用的有效治疗方法有限。细胞免疫疗法，如嵌合抗原受体（CAR）T细胞疗法，在治疗血液系统恶性肿瘤方面取得了显著成功。然而，CAR T细胞疗法在胰腺癌中的疗效一直有限。本综述概述了目前正在进行的胰腺癌CAR T细胞临床研究，以及提高CAR T细胞疗效的主要挑战和策略。这些策略包括武装CAR T细胞；开发现成的同种异体CAR T细胞；使用其他免疫CAR细胞，如自然杀伤细胞和肿瘤浸润淋巴细胞；以及联合治疗。仔细纳入临床前模型将加强对受影响个体的管理，有助于细胞免疫疗法的纳入。需要一种涉及细胞免疫疗法治疗的多方面、个性化方法来改善胰腺癌的治疗结果。
