Ward Stephen, Casey David, Labarthe Marie-Christine, Whelan Michael, Dalgleish Angus, Pandha Hardev, Todryk Stephen
Onyvax Ltd., St George's Hospital Medical School, London, UK.
Cancer Immunol Immunother. 2002 Sep;51(7):351-7. doi: 10.1007/s00262-002-0286-2. Epub 2002 Jun 14.
Despite the identification of tumour antigens and their subsequent generation in subunit form for use as cancer vaccines, whole tumour cells remain a potent vehicle for generating anti-tumour immunity. This is because tumour cells express an array of target antigens for the immune system to react against, avoiding problems associated with major histocompatibility complex (MHC)-restricted epitope identification for individual patients. Furthermore, whole cells are relatively simple to propagate and are potentially efficient at contributing to the process of T cell priming. However, whole cells can also possess properties that allow for immune evasion, and so the question remains of how to enhance the immune response against tumour cells so that they are rejected. Scenarios where whole tumour cells may be utilised in immunotherapy include autologous tumour cell vaccines generated from resected primary tumour, allogeneic (MHC-disparate) cross-reactive tumour cell line vaccines, and immunotherapy of tumours in situ. Since tumour cells are considered poorly immunogenic, mainly because they express self-antigens in a non-stimulatory context, the environment of the tumour cells may have to be modified to become stimulatory by using immunological adjuvants. Recent studies have re-evaluated the relative roles of direct and cross-priming in generating anti-tumour immunity and have highlighted the need to circumvent immune evasion.
尽管已鉴定出肿瘤抗原并随后将其制备成亚单位形式用作癌症疫苗,但完整肿瘤细胞仍是产生抗肿瘤免疫的有效载体。这是因为肿瘤细胞表达一系列可供免疫系统作出反应的靶抗原,避免了与针对个体患者的主要组织相容性复合体(MHC)限制性表位鉴定相关的问题。此外,完整细胞相对易于增殖,并且在促进T细胞启动过程中可能效率较高。然而,完整细胞也可能具有允许免疫逃逸的特性,因此如何增强针对肿瘤细胞的免疫反应以使其被排斥的问题仍然存在。完整肿瘤细胞可用于免疫治疗的情况包括由切除的原发性肿瘤产生的自体肿瘤细胞疫苗、同种异体(MHC不相合)交叉反应性肿瘤细胞系疫苗以及原位肿瘤的免疫治疗。由于肿瘤细胞被认为免疫原性较差,主要是因为它们在非刺激环境中表达自身抗原,因此可能必须通过使用免疫佐剂来改变肿瘤细胞的环境以使其具有刺激作用。最近的研究重新评估了直接启动和交叉启动在产生抗肿瘤免疫中的相对作用,并强调了规避免疫逃逸的必要性。