HPV-Targeted Adoptive T-cell Therapy Induces Regression in Metastatic Cervical Cancer

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HPV-Targeted Adoptive T-cell Therapy Induces Regression in Metastatic Cervical Cancer
HPV-Targeted Adoptive T-cell Therapy Induces Regression in Metastatic Cervical Cancer

CHICAGO, IL—Durable, complete tumor regression can occur following a single infusion of human papillomavirus tumor-infiltrating lymphocytes (HPV-TIL) in women with metastatic cervical cancer, a small, proof-of-concept study reported at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.

These results show that an immunotherapy can induce regression of cervical cancer and that adoptive T-cell therapy can mediate regression of an epithelial cancer, said Christian S. Hinrichs, MD, an assistant clinical investigator at the National Cancer Institute, Bethesda, MD.

To date, immunotherapy has not been effective in metastatic cervical cancer, which causes more than 4,000 deaths in the United State annually. Chemotherapy is not curative and rarely provides durable palliation.

Dr. Hinrichs said adoptive T-cell therapy is an emerging platform for the “highly personalized” treatment of cancer. This therapy, based on the infusion of autologous tumor-targeted T cells, has resulted in durable complete tumors responses in both melanoma and B-cell malignancies; however, study in epithelial cancers has been limited.

Dr. Christian S. HinrichsChristian S. Hinrichs, MD

“We initiated a clinical trial to treat metastatic HPV-positive cancers with tumor-infiltrating lymphocytes selected for HPV E6- and E7-reactivity,” he said. The HPV-TIL infusion was preceded by non-myeloablative conditioning with cyclophosphamide 60 mg/kg , administered twice, plus fludarabine 25 mg/m2, administered five times, followed by high-dose bolus aldesleukin.

A total of nine patients were treated, receiving a median of 81 x 109 T cells (range, 33 to 159 x 109 T cells) as a single infusion. The patients ranged in age from 30 to 59 years and predominantly had HPV-18; five of the patients had adenosquamous histology and four, squamous histology.

In six of eight patients, the infused cells possessed reactivity against high-risk HPV E6 and/or E7. Two patients with no HPV reactivity did not respond to treatment or display repopulation with HPV-reactive T cells.

Three of the six patients with HPV reactivity demonstrated objective tumor responses—two complete responses (CRs) and one partial response—the latter with a 39% reduction in tumor volume. The two patients with CRs had widespread metastases; responses are ongoing at 22-plus and 15-plus months after treatment.

RELATED: Gynecologic Cancers Resource Center

Grade 3/4 adverse events (AEs) included lymphopenia, leukopenia, neutropenia, anemia, and thrombocytopenia in all nine patients and febrile neutropenia in five. Other AEs include infection in six patients, metabolic disorders in five, and nausea/vomiting in four patients.

He said that this study will be expanded to enroll additional patients, and continued study of HPV-TIL for metastatic cervical cancer is warranted. The same study is also exploring adoptive T-cell therapy for treatment of other HPV-related cancers, such as throat cancer and anal cancer.

Reference

  1. Hinrichs CS, Stevanovic S, Draper L et al. Abstract LBA3008. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.

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