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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.Perspective
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These are young women who had failed multiple attempts at directed therapy to the cancer cells. Here is proof of principle that, by ignoring the cancer cell but activating these T cells, we can — in a few of these patients — produce durable responses.
This approach in melanoma has been well studied, and in up to 50% of carefully selected melanoma patients, you can tease out their T cells and expand them in them laboratory, modify them genetically, and give them back with high-dose interleukin-2. So this is a well-established approach in selected patients with melanoma.
What’s different here is that we’re actually moving it into a disease that’s generally not seen well by the immune system, but we’re using these oncoproteins of the HPV virus to tease out the T cells from which the virus particles provoke a response. It’s a very exciting approach that has implications for other HPV-associated solid tumors.
Perspective
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It’s very difficult to do studies in patients with cervical carcinoma, so I encourage patients in this situation to seek out this federally funded trial at the NCI. We met as a group of thought leaders in gynecologic oncology and we published a state of the science in cancer. We highlighted this work with immunotherapy in cervical carcinoma, so this is one of the areas we believe is going to be one of the most promising for this field. But we will need intentional help to prove the concepts seen here, which I believe are very exciting.
It is my hope … that we are going to look at immunotherapy as the future for cervical carcinoma treatments. The best we have commits women to chemotherapy and/or a biologic therapy for the rest of their lives, which is no more than 2 years for the majority of these young women. So if we can harvest a way to scale this up so that at least across academic centers — if not community hospitals — we could standardize this approach and identify the patients most likely to benefit, we could really reduce deaths from this disease.