Division of Hematology-Oncology, Hôpital Maisonneuve-Rosemont Research Center, Montreal, Canada; Department of Medicine, Université de Montréal, Montreal, Canada.
Division of Hematology-Oncology, Hôpital Maisonneuve-Rosemont Research Center, Montreal, Canada; Department of Medicine, Université de Montréal, Montreal, Canada; Department of Microbiology, Infectiology and Immunology, Université de Montréal, Canada.
Semin Immunol. 2019 Apr;42:101306. doi: 10.1016/j.smim.2019.101306.
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.
癌症的发展通常意味着免疫系统无法识别肿瘤抗原并杀死恶性细胞。虽然整个免疫细胞库很广泛，但能够对单个肿瘤抗原产生反应的免疫细胞通常非常有限。癌症免疫疗法的目的是增强免疫系统的力量、数量和质量，使其能够轻易地识别和消除癌细胞。随着免疫疗法向更个性化的医学转变，不同类型的肿瘤抗原可以用作靶抗原，使 T 细胞能够破坏肿瘤细胞。这些抗原主要被定义为肿瘤相关抗原（TAA）、新抗原或次要组织相容性抗原。它们的临床应用包括直接注射 TAA 和新抗原、在疫苗接种方法中给予负载肽的树突状细胞，或输注体外扩增的肿瘤特异性 T 细胞。然而，这些细胞疗法面临着几个挑战，包括免疫抑制性肿瘤微环境、体外扩增的抗原特异性 T 细胞缺乏持久性以及这些疗法的潜在脱靶毒性。在这篇综述中，我们将讨论允许更好地扩增肿瘤反应性 T 细胞的最新进展以及用于克服癌症细胞疗法面临的挑战的新策略。
