Mulla Nihal, Chablani Lipika, Parenky Ashwin C, D'Souza Martin J
Department of Pharmaceutical & Administrative Sciences, College of Pharmacy & Health Sciences, Western New England University, Springfield, MA 01119, USA.
Department of Pharmaceutical Sciences, Wegmans School of Pharmacy, St. John Fisher University, Rochester, NY 14618, USA.
Vaccines (Basel). 2023 Feb 24;11(3):543. doi: 10.3390/vaccines11030543.
Tumor cells express antigens that should induce immune-mediated rejection; however, spontaneous rejection of established tumors is rare. Recent evidence suggests that patients suffering from cancer exhibit an elevation in regulatory T cells population, a subset of CD4+ T cells, which suppress tumor recognition and elimination by cytotoxic T cells. This study investigates immunotherapeutic strategies to overcome the immunosuppressive effects exerted by regulatory T cells. A novel immunotherapeutic strategy was developed by simultaneous administration of oral microparticulate breast cancer vaccines and cyclophosphamide, a regulatory T cell inhibitor. Breast cancer vaccine microparticles were prepared by spray drying, and administered orally to female mice inoculated with 4TO7 murine breast cancer cells in combination with a low dose of intraperitoneally administered cyclophosphamide. Mice receiving the combination of vaccine microparticles and cyclophosphamide exhibited maximal tumor regression and the highest survival rate compared with the control groups. This study highlights the importance of cancer vaccination along with regulatory T cell depletion in cancer therapy, and suggests that a low dose of cyclophosphamide that specifically and significantly depletes regulatory T cells may be a highly effective immunotherapeutic strategy for the treatment of cancer.
肿瘤细胞表达的抗原应能诱导免疫介导的排斥反应；然而，已形成的肿瘤发生自发排斥的情况很少见。最近的证据表明，癌症患者体内调节性T细胞（CD4 + T细胞的一个亚群）数量增加，这些细胞会抑制细胞毒性T细胞对肿瘤的识别和清除。本研究旨在探究克服调节性T细胞所产生免疫抑制作用的免疫治疗策略。通过同时给予口服微粒型乳腺癌疫苗和环磷酰胺（一种调节性T细胞抑制剂），开发出了一种新型免疫治疗策略。乳腺癌疫苗微粒通过喷雾干燥制备，并口服给予接种了4TO7小鼠乳腺癌细胞的雌性小鼠，同时腹腔注射低剂量的环磷酰胺。与对照组相比，接受疫苗微粒和环磷酰胺联合治疗的小鼠肿瘤消退最为明显，生存率也最高。本研究强调了癌症疫苗接种以及在癌症治疗中消耗调节性T细胞的重要性，并表明低剂量的环磷酰胺能特异性且显著地消耗调节性T细胞，可能是一种治疗癌症的高效免疫治疗策略。
