Towards effective immunotherapy of cancer using genetically enhanced lymphocytes

免疫疗法是一种潜在的强大而特殊的癌症治疗形式，可能比目前的治疗形式（包括化疗和放疗）更有效，副作用更少。在接受某些恶性肿瘤免疫治疗的一部分患者中已经观察到显著的反应，但这些反应都太少见了。T细胞是免疫系统的重要组成部分，但它们往往不能识别癌症，也不能对肿瘤做出足够强烈的反应。该项目研究了通过对T细胞进行基因改造，使患者的T细胞具有识别癌症和积极对抗癌症的能力的可行性。在这项研究中，从患有癌症的老鼠身上取出T细胞，并将编码抗癌分子的基因插入T细胞中。这些T细胞被激活，大量生长，然后再给荷瘤小鼠注射强化疫苗。所采用的策略是新颖的，拟议的研究以及初步数据代表了世界上此类调查的第一次。从这些研究中获得的信息将扩展我们对肿瘤免疫学的理解，并提供对实现抗肿瘤反应的各种参数的重要性的赞赏。通过这些原理验证的临床前模型的研究，提高了抗肿瘤反应，可以为患者提供更有效的免疫治疗方案。

Immunotherapy is a potentially powerful and specific form of cancer therapy that may be more effective and have fewer side effects than current forms of therapy including chemotherapy and radiotherapy. Already dramatic responses have been observed in a proportion of patients receiving immunotherapy for some malignancies but these responses are all too infrequent. T cells constitute an important part of the immune system but they often fail to recognize cancer and do not respond strongly enough against tumours. This project investigates the feasibility of endowing patients' T cells with the abilities to recognize cancer and respond vigorously against it by genetically modifying the T cells. In this study, T cells are removed from mice that have cancer and a gene encoding an anti-cancer molecule inserted into the T cells. The T cells are activated, grown to large numbers and given back to tumour-bearing mice followed by booster vaccinations. The strategy used is novel and the proposed studies, together with preliminary data, represent the first investigations of their type in the world. Information derived from these studies will extend our understanding of tumour immunology and provide an appreciation of the importance of various parameters in achieving anti-tumour responses. Improved anti-tumour responses achieved through investigations in these proof-of-principle pre-clinical models could lead to more effective immunotherapeutic regimens in patients.