Tumor infiltrating lymphocyte therapy for human papillomavirus-positive cancers

本项目的目的是确定TIL治疗HPV阳性肿瘤的客观临床有效率，并探讨HPV阳性肿瘤TIL在体内外的特异性、表型和功能。我们的实验室已经确定了从HPV阳性的癌症中产生临床分级和规模的TIL的可行性。在此基础上，我们进行了一项针对HPV阳性癌症患者的TIL的临床试验。目前正在进行实验室研究，以确定HPV-TIL的特征，并为这一疾病家族创新下一代细胞疗法。我们在《临床肿瘤学杂志》上报道，在接受该方案治疗的宫颈癌患者中，有2/9的患者肿瘤完全消退。这项研究是迄今为止第一项也是唯一一项证明过继T细胞治疗后上皮癌完全消退的研究。我们还在《科学》杂志上报道，在这项临床试验中，持久的、完整的肿瘤反应与靶向HPV和非HPV抗原有关。这一发现改变了HPV+癌症免疫治疗的范式，强调了非病毒抗原靶点的潜在重要性。

The purpose of this project is to determine the objective clinical response rate of TIL therapy in HPV-positive cancers and to investigate the specificity, phenotype, and function of TIL from HPV-positive cancers in vitro and in vivo. Our laboratory has established the feasibility of generating TIL from HPV-positive cancers at clinical grade and scale. Based on that work we have conducted a clinical trial of TIL from HPV-positive cancers (HPV-TIL). Laboratory studies to characterize HPV-TIL and to innovate the next generate of cellular therapies for this family of diseases are ongoing. We have reported in the Journal of Clinical Oncology that complete tumor regression occurred in 2/9 women with cervical cancer treated on this protocol. This study was the first and only study thus far to demonstrate complete regression of an epithelial cancer following adoptive T-cell therapy. We have also reported in Science that durable, complete tumor responses in this clinical trial were linked to the targeting of HPV and non-HPV antigens. This finding changes the paradigm for immunotherapy of HPV+ cancers to emphasize the potential importance of non-viral antigen targets.