HPV-targeted T-cell therapy may induce cervical cancer regression

1. In a small, prospective trial of nine patients with metastatic cervical cancer, three patients demonstrated complete or partial response after a single infusion of T-cells reactive to HPV oncoproteins.

Evidence Rating Level: 3 (Average)    

Study Rundown: Although the use of human papillomavirus (HPV) vaccination and screening programs may significantly reduce the risk of cervical cancer, it remains the cause of death for more than 4000 women annually in the United States. Patients presenting with advanced disease are often refractory to chemotherapy and face significant morbidity and mortality. Adoptive T-cell therapy (ACT), which involves infusion of autologous tumor-reactive T-cells, has previously been demonstrated to produce clinical responses in patients with B-cell malignancies and melanoma. The purpose of this study was to determine the efficacy of ACT in HPV-associated cervical cancer. Nine patients with advanced/metastatic cervical cancer were recruited and treated with infusion of autologous T-cells reactive to HPV oncoproteins (HPV-TILs). At the conclusion of the trial, the authors found that 3 of the 9 women enrolled demonstrated an objective tumor response after a single infusion of T-cells (two complete response and one partial response). Both patients who demonstrated complete response demonstrated on-going response 22 and 15 months post-treatment. No acute toxicities with infusion of HPV-TILs were reported. The results of this trial provide strong proof-of-concept evidence of the use of ACT in cervical cancer. However, given the small size of the study cohort, the exact biomarker of the mechanism within individual HPV-TILs remains unclear. Additional large, prospective trials are required to accurately delineate this effect.

Click to read the study in JCO

Relevant Reading: Exploiting the curative potential of adoptive T-cell therapy for cancer

In-Depth [prospective cohort]: Nine patients (median age 37 years) with pathologically confirmed metastatic/locally advanced refractory or recurrent cervical cancer who had previously undergone platinum-based chemotherapy or chemoradiotherapy were enrolled in the current study. The distribution of the patients’ tumors were squamous cell carcinoma (n=4), adenocarcinoma (n=2), and adenosquamous carcinoma (n=2). The distribution of HPV serotype was HPV-18 (n=7) and HPV-16 (n=2). All patients underwent a protocol consisting of a lymphocyte-depleting chemotherapy regimen with cyclophosphamide and fludarabine, followed by HPV-TIL infusion and aldesleukin. The primary outcomes were tumor response, both complete and partial, while secondary outcomes included adverse events and HPV reactivity in the patients. Three of the 9 patients achieved objective tumor response; 2 patients with complete response demonstrated ongoing response 22 and 15 months after treatment. The most common severe toxicities were hematologic (i.e. anemia and leukopenia) and were related to the lymphocyte-deplete chemotherapy regimen. The frequency of HPV reactivity in the T-cell infusions was measured by interferon gamma production, ELISPOT, and CD137 up-regulation assays, and was positively correlated with tumor response (p = 0.0238). HPV reactivity in the patients, as assessed by interferon gamma production, was associated with objective tumor response (p = 0.0238).

Image: PD

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