HPV-targeted T-cell therapy shows promise for advanced cervical cancer
CHICAGO — HPV-targeted tumor-infiltrating lymphocytes demonstrated encouraging activity in patients with advanced cervical cancer, according to results of a phase 2 study presented at the ASCO Annual Meeting.
“While it’s hoped that vaccines and screening will reduce the future incidence of cervical cancer, at the present time in the United States it causes the deaths of more than 4,000 women each year,” researcher Christian Hinrichs, MD, assistant clinical investigator at the NCI, said during a press conference. “Chemotherapy for advanced cervical cancer is not curative and really provides durable palliation, so better treatments are desperately needed.”
Previous research has shown adoptive T-cell therapy is active in melanoma, leukemia and sarcoma; however, this is the first study to demonstrate the therapy’s promise in cervical cancer, Hinrichs said.
“Cervical cancers harbor attractive therapeutic targets for immunotherapy in the E6 and E7 oncoproteins, but trials of immunotherapy for this disease have been disappointing up until this time,” Hinrichs said.
The analysis included nine patients who received a single median infusion of 81 x 109 T cells selected for HPV E6 and E7 reactivity. Patients underwent non-myeloablative conditioning before their infusion, and high-dose bolus aldesleukin after their infusion.
The infused T cells demonstrated anti-HPV E6/7 reactivity in six patients, three of whom demonstrated a response.
One patient achieved a partial response with a 39% reduction in tumor volume.
Two patients achieved a complete remission — one with HPV16-positive squamous cell carcinoma and the other with chemoradiation-refractory HPV18-positive adenocarcinoma. Both had widespread metastatic disease at baseline and were heavily pretreated. One patient remained in remission for 22 months, and the other remained in remission for 15 months.
Researchers observed prolonged repopulation of HPV-reactive T cells after treatment. Increased frequencies of the T cells were detected at 13 months in one patient, and 6 months in the other.
“This study shows that durable and complete remission can occur following a single infusion of HPV-targeted tumor infiltrating T cells, and it provides proof of principle that an immunotherapy can cause regression of cervical cancer,” Hinrichs said. “Adoptive T-cell therapy can mediate regression of an epithelial cancer.”
For more information:
Hinrichs CS. Abstract #LBA3008. Presented at: ASCO Annual Meeting; May 30-June 1, 2014; Chicago.Disclosure: The study was funded by the NIH. The researchers report no relevant financial disclosures.