Chodon Thinle, Koya Richard C, Odunsi Kunle
a Center for Immunotherapy and.
b Department of Gynecologic Oncology , Roswell Park Cancer Institute , Buffalo, NY , USA.
Immunol Invest. 2015;44(8):817-36. doi: 10.3109/08820139.2015.1096684.
Clinical progress in the field of cancer immunotherapy has been slow for many years but within the last 5 years, breakthrough successes have brought immunotherapy to the forefront in cancer therapy. Promising results have been observed in a variety of cancers including solid tumors and hematological malignancies with adoptive cell therapy using natural host tumor infiltrating lymphocytes, host cells that have been genetically engineered with antitumor T-cell receptors or chimeric antigen receptors, immune checkpoint inhibitors like anti-CTLA-4, anti-PD-1 or PD-L1 monoclonal antibodies and oncolytic virus-based immunotherapy. However, most treatment modalities have shown limited efficacy with single therapy. The complex nature of cancer with intra- and inter-tumor antigen and genomic heterogeneity coupled with the immune suppressive microenvironment emphasizes the prospect of personalized targeted immunotherapy to manipulate the patient's own immune system against cancer. For successful, robust and long-lasting cure of cancer, a multi-modal approach is essential, combining anti-tumor cell therapy with manipulation of multiple pathways in the tumor microenvironment to ameliorate tumor-induced immunosuppression.
多年来,癌症免疫治疗领域的临床进展一直缓慢,但在过去5年里,突破性的成功使免疫治疗在癌症治疗中占据了前沿位置。在多种癌症中都观察到了有前景的结果,包括实体瘤和血液系统恶性肿瘤,采用的治疗方法有利用天然宿主肿瘤浸润淋巴细胞的过继性细胞疗法、经抗肿瘤T细胞受体或嵌合抗原受体基因工程改造的宿主细胞、抗CTLA-4、抗PD-1或PD-L1单克隆抗体等免疫检查点抑制剂以及基于溶瘤病毒的免疫治疗。然而,大多数治疗方式单药治疗时疗效有限。癌症具有肿瘤内和肿瘤间抗原及基因组异质性的复杂特性,再加上免疫抑制性微环境,这凸显了个性化靶向免疫治疗的前景,即操控患者自身免疫系统对抗癌症。为了成功、有力且持久地治愈癌症,多模式方法至关重要,将抗肿瘤细胞疗法与操控肿瘤微环境中的多种途径相结合,以改善肿瘤诱导的免疫抑制。