子宮頸がんにおけるT細胞免疫療法（Abstract: LBA3008）

A small phase II study shows striking results in several women with advanced cervical cancer, using a new type of personalized immunotherapy, known as adoptive T-cell therapy. In the study, two patients with widespread metastases had complete remissions after a single treatment with the HPV-targeted T-cells, and have been cancer free for nearly a year or longer.

"This proof-of-principal study shows that adoptive transfer of HPV-targeted T-cells can cause complete remission of metastatic cervical cancer and that this remission can be long-lasting," said lead study author Christian Hinrichs, M.D., an assistant clinical investigator at the National Cancer Institute in Bethesda, M.D.. "One implication of the study is that cellular therapy might have application to a broader range of tumor types than previously recognized. This treatment is still considered experimental and is associated with significant side effects. We also need to explore why this therapy worked so well in certain women, and not in others."

Women with metastatic cervical cancer – caused by the human papillomavirus (HPV) – have limited treatment options. The median survival with the two standard first-line therapies, chemotherapy and a combination of chemotherapy and bevacizumab, is 13 and 17 months, respectively. No second-line treatments that improve survival are available.

HPV-targeted adoptive T-cell therapy essentially augments the natural immune response to HPV in the tumor. To develop the therapy, HPV-targeted T-cells are grown from a patient's tumor in the laboratory. Those cells are subsequently infused back into the patient to fight the cancer. This is the first time adoptive T-cell therapy has been tested in cervical cancer; it has previously shown promise in melanoma, leukemia, and sarcoma.

In the study, nine patients received adoptive T-cell therapy, and three responded to the treatment. One patient had a partial response, with a 39-percent reduction in tumor volume, and two patients had complete remissions. Those two patients had widespread metastases, and the disease had progressed despite prior therapy. At the time of analysis, those patients remained in remission for 11 and 18 months after treatment. The treatment was associated with serious side effects, the most common being low blood counts, infections, and metabolic disorders.

Researchers are planning to expand this study to enroll additional patients. The same study is also exploring adoptive T-cell therapy for treatment of other HPV-related cancers, such as throat cancer and anal cancer.

Adoptive T-cell therapy is being offered at an increasing number of major medical centers in the United States and other countries. Along with screening and preventative vaccines, better treatments are needed to reduce cervical cancer deaths in the future.

"Novel treatments are needed for women with recurrent or metastatic cervical cancer. Because of the association between cervical cancer and the HPV virus, adoptive immunotherapy is a promising approach for these patients," said Don S. Dizon, M.D., FACP, ASCO Expert. "These preliminary data demonstrate, not only the viability of this approach, but that gains in survival can be realized in a cancer where patients have little to no effective treatment options and where median survival is usually less than two years."

This research was supported by the National Cancer Institute, National Institutes of Health.