Adoptive T-cell Therapy Has Clinical Activity in Metastatic Cervical Cancer

Metastatic cervical cancer is a chemorefractory, generally incurable disease for which immunotherapy may hold promise because the vast majority of cervical cancers harbor immunogenic human papillomavirus (HPV) antigens. In an exploratory study in 9 patients with metastatic cervical cancer, Stevanović and colleagues evaluated whether a single intravenous infusion of autologous tumor-infiltrating lymphocytes enriched for those with reactivity against the HPV antigens E6 and E7 could induce tumor regression. Objective responses were observed in 3 of the 9 patients, including 2 patients who experienced complete regressions at all sites of disease and remained disease-free 15 and 22 months after treatment. No acute toxicity was observed, and the most common adverse events were hematologic and thought to be due to the single cycle of lymphocyte-depleting conditioning chemotherapy administered prior to adoptive T-cell transfer. Autoimmune adverse events were not observed and no patients experienced severe cytokine release syndrome. The frequency and degree of reactivity of HPV-reactive T cells, as measured by IFNγ production and CD137 upregulation, was highest in the 3 patients who experienced objective responses and was significantly correlated with clinical response overall. The responders also had the highest frequency of HPV-reactive T cells in their peripheral blood, and clinical response was correlated with the frequency of HPV-reactive T cells in the peripheral blood 1 month after adoptive T-cell transfer. The frequency of HPV-reactive T cells remained elevated in the responding patients at later timepoints after treatment, further suggesting that the adoptively transferred HPV-reactive T cells contributed to the clinical responses, although a role for infused tumor-infiltrating lymphocytes targeting different tumor antigens cannot be excluded. In addition to providing support for further evaluation of adoptive T-cell therapy in patients with metastatic cervical cancer, these results indicate that durable, complete responses to adoptive T-cell therapy can be achieved in an epithelial malignancy.

Stevanović S, Draper LM, Langhan MM, Campbell TE, Kwong ML, Wunderlich JR, et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus–targeted tumor-infiltrating T cells. J Clin Oncol 2015 Mar 30 [Epub ahead of print].

Note: Research Watch is written by Cancer Discovery Science Writers. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://CDnews.aacrjournals.org.