T-Cell Therapy for Cervical Cancer

Pitting the immune system against human papillomavirus (HPV) may be a promising strategy for treating women with advanced cervical cancer, according to a small, federally funded phase II study. The results were reported by Christian Hinrichs, MD, an assistant clinical investigator at the NCI in Bethesda, MD, during the American Society of Clinical Oncology's Annual Meeting in Chicago, IL, May 30–June 3.

More than 4,000 women in the United States die from cervical cancer each year. Their median survival is 13 months on chemotherapy and 17 months if bevacizumab (Avastin; Roche) is added.

In this study, researchers used an approach called tumor-infiltrating lymphocyte (TIL) therapy, which has had some success in treating metastatic melanoma and B-cell malignancies. They isolated T cells from patients' tumors and selected those with reactivity with HPV oncoproteins E6 and E7. The TILs were then expanded and infused back into each patient, along with IL2, a T-cell growth factor.

All 9 patients in the study had either HPV-16 or HPV-18 infections, which together cause about 80% of cervical cancers. Two women with widespread metastases and chemotherapy-resistant disease achieved complete and lasting remissions of 11 and 18 months, respectively, at the time of analysis.

“This provides the first proof-of-principle that HPV-targeted TIL therapy can induce regression in cervical cancer,” Hinrichs said.

Hinrichs cautioned that HPV-TIL therapy “is still considered experimental and associated with significant side effects,” mainly bone marrow suppression and an increased infection risk due to neutropenia. However, he added, “these toxicities are fully reversible, and it's a one-time treatment.”

One challenge associated with personalized immunotherapy is that the antigens targeted by T cells often exist in cells elsewhere in the body, not just in cancer cells. However, the E6 and E7 viral oncoproteins make “extremely attractive targets,” said Hinrichs, because they are expressed only in infected tissue.

The study's results are limited but striking. “These are young women who failed multiple attempts at tumor-directed therapy,” said Steven O'Day, MD, an immunologist at the University of Southern California's Keck School of Medicine in Los Angeles. “By ignoring the cancer cells and, instead, activating T cells, we've provoked a few durable responses in a disease generally not seen well by the immune system.”

Hinrichs is now exploring why this therapy was highly effective in only some women. “The next step, to better clarify the response rate, is to treat more patients—we're expanding to 35,” he said. “We've also added a patient cohort with noncervical, HPV-positive cancers to this study.

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