Complete Regression of Metastatic Cervical Cancer After Treatment With Human Papillomavirus–Targeted Tumor-Infiltrating T Cells

Abstract

Purpose Metastatic cervical cancer is a prototypical chemotherapy-refractory epithelial malignancy for which better treatments are needed. Adoptive T-cell therapy (ACT) is emerging as a promising cancer treatment, but its study in epithelial malignancies has been limited. This study was conducted to determine if ACT could mediate regression of metastatic cervical cancer. Patients and Methods Patients enrolled onto this protocol were diagnosed with metastatic cervical cancer and had previously received platinum-based chemotherapy or chemoradiotherapy. Patients were treated with a single infusion of tumor-infiltrating T cells selected when possible for human papillomavirus (HPV) E6 and E7 reactivity (HPV-TILs). Cell infusion was preceded by lymphocyte-depleting chemotherapy and was followed by administration of aldesleukin. Results Three of nine patients experienced objective tumor responses (two complete responses and one partial response). The two complete responses were ongoing 22 and 15 months after treatment, respectively. One partial response was 3 months in duration. The HPV reactivity of T cells in the infusion product (as measured by interferon gamma production, enzyme-linked immunospot, and CD137 upregulation assays) correlated positively with clinical response (P = .0238 for all three assays). In addition, the frequency of HPV-reactive T cells in peripheral blood 1 month after treatment was positively associated with clinical response (P = .0238). Conclusion Durable, complete regression of metastatic cervical cancer can occur after a single infusion of HPV-TILs. Exploratory studies suggest a correlation between HPV reactivity of the infusion product and clinical response. Continued investigation of this therapy is warranted.

Attitudes Towards Human Papilloma Virus Vaccination in the Latin American Andean Region

“…Acknowledgement of vaccinator training for safe vaccine administration and reassurance of expected minor adverse effects including injection site pain should be included in public education campaigns [37]. Peruvians' awareness that vaccines may be preventive or therapeutic will be beneficial in the future should the therapeutic vaccines and adoptive T-cell therapies currently under investigation for cervical intraepithelial neoplasia 2/3 and CC treatment reach the market [44,45].…”

Lymphoepithelioma-like gastric carcinoma located in the lesser curvature of the gastric body: A case report and review of the literature

“…Since most gastric LELCs contain the EBV oncoproteins, and cancer-driving viral antigens are highly attractive therapeutic targets, therapeutic vaccines targeting the EBV oncoproteins may prove to be beneficial. Furthermore, adoptive T-cell therapy is emerging as a promising cancer treatment, and one recently published study demonstrated that durable, complete regression of metastatic cervical cancer may occur after a single infusion of HPV-targeted tumor-infiltrating lymphocytes (TILs) (18). Hence, we must investigate whether an infusion of EBV-targeted TILs may induce cancer regression in patients with gastric LELC.…”

Prevalence and Distribution of High-Risk Human Papillomavirus Genotypes in Invasive Carcinoma of the Uterine Cervix in Uruguay. An update on clinical outcome

“…In CC a large polyclonal repertoire of T cells HPVspecific have been demonstrated within the total population of TILs as well as in tumor-draining lymph nodes (de Vos van Steenwijk, 2010). In a therapeutic approach, objective regression of metastasis in CC patients by HPV-TILs enables to discuss about their immunological role, which could explain more aggressive behavior in HPV-negative tumors and encourages research for immunotherapy strategies in CC (Stevanović, 2015).…”