Medina Rogelio, Wang Herui, Caisová Veronika, Cui Jing, Indig Iris H, Uher Ondrej, Ye Juan, Nwankwo Anthony, Sanchez Victoria, Wu Tianxia, Nduom Edjah, Heiss John, Gilbert Mark R, Terabe Masaki, Ho Winson, Zenka Jan, Pacak Karel, Zhuang Zhengping
Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States.
David Geffen School of Medicine, University of California, Los Angeles, California, United States.
Adv Ther (Weinh). 2020 Sep;3(9). doi: 10.1002/adtp.202000044. Epub 2020 Jun 9.
Emerging evidence is demonstrating the extent of T-cell infiltration within the tumor microenvironment has favorable prognostic and therapeutic implications. Hence, immunotherapeutic strategies that augment the T-cell signature of tumors hold promising therapeutic potential. Recently, immunotherapy based on intratumoral injection of mannan-BAM, toll-like receptor ligands and anti-CD40 antibody (MBTA) demonstrated promising potential to modulate the immune phenotype of injected tumors. The strategy promotes the phagocytosis of tumor cells to facilitate the recognition of tumor antigens and induce a tumor-specific adaptive immune response. Using a syngeneic colon carcinoma model, we demonstrate MBTA's potential to augment CD8 T-cell tumor infiltrate when administered intratumorally or subcutaneously as part of a whole tumor cell vaccine. Both immunotherapeutic strategies proved effective at controlling tumor growth, prolonged survival and induced immunological memory against the parental cell line. Collectively, our investigation demonstrates MBTA's potential to trigger a potent anti-tumor immune response.
新出现的证据表明,肿瘤微环境中T细胞浸润的程度具有良好的预后和治疗意义。因此,增强肿瘤T细胞特征的免疫治疗策略具有广阔的治疗潜力。最近,基于瘤内注射甘露聚糖-BAM、Toll样受体配体和抗CD40抗体(MBTA)的免疫疗法显示出调节注射肿瘤免疫表型的潜在前景。该策略促进肿瘤细胞的吞噬作用,以利于肿瘤抗原的识别并诱导肿瘤特异性适应性免疫反应。利用同基因结肠癌模型,我们证明了MBTA作为全肿瘤细胞疫苗的一部分进行瘤内或皮下给药时,具有增强CD8 T细胞肿瘤浸润的潜力。两种免疫治疗策略在控制肿瘤生长、延长生存期以及诱导针对亲本细胞系的免疫记忆方面均被证明是有效的。总体而言,我们的研究证明了MBTA触发强效抗肿瘤免疫反应的潜力。