Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA.
J Immunol. 2011 Nov 15;187(10):4935-46. doi: 10.4049/jimmunol.1102095. Epub 2011 Oct 17.
Optimum efficacy of therapeutic cancer vaccines may require combinations that generate effective antitumor immune responses, as well as overcome immune evasion and tolerance mechanisms mediated by progressing tumor. Previous studies showed that IL-13Rα2, a unique tumor-associated Ag, is a promising target for cancer immunotherapy. A targeted cytotoxin composed of IL-13 and mutated Pseudomonas exotoxin induced specific killing of IL-13Rα2(+) tumor cells. When combined with IL-13Rα2 DNA cancer vaccine, surprisingly, it mediated synergistic antitumor effects on tumor growth and metastasis in established murine breast carcinoma and sarcoma tumor models. The mechanism of synergistic activity involved direct killing of tumor cells and cell-mediated immune responses, as well as elimination of myeloid-derived suppressor cells and, consequently, regulatory T cells. These novel results provide a strong rationale for combining immunotoxins with cancer vaccines for the treatment of patients with advanced cancer.
最佳疗效的治疗性癌症疫苗可能需要联合应用，以产生有效的抗肿瘤免疫反应，同时克服进展性肿瘤介导的免疫逃逸和耐受机制。先前的研究表明，白细胞介素 13 受体α2（IL-13Rα2）是一种独特的肿瘤相关抗原，是癌症免疫治疗的一个很有前途的靶点。由白细胞介素 13 和突变型绿脓杆菌外毒素组成的靶向细胞毒素可诱导特异性杀伤 IL-13Rα2（+）肿瘤细胞。令人惊讶的是，当与 IL-13Rα2 DNA 癌症疫苗联合使用时，它在已建立的小鼠乳腺癌和肉瘤肿瘤模型中对肿瘤生长和转移具有协同的抗肿瘤作用。协同作用的机制涉及肿瘤细胞的直接杀伤和细胞介导的免疫反应，以及髓源抑制细胞和调节性 T 细胞的消除。这些新的结果为将免疫毒素与癌症疫苗联合用于治疗晚期癌症患者提供了强有力的依据。
