Combination Immunotherapy Approach Offers Clinical Benefit in Recurrent Ovarian Cancer

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(ChemotherapyAdvisor) – Combining dendritic cell-based autologous whole tumor antigen vaccination with adoptive lymphocyte transfer using tumor antigen-specific T cells shows promise in treating women with recurrent ovarian cancer, according to research presented at the American Association for Cancer Research (AACR) Annual Meeting 2013, in Washington, DC.

“This immunotherapeutic strategy has two steps—dendritic cell vaccination and adoptive T-cell therapy. This is the first time such a combination immunotherapy approach has been used for patients with ovarian cancer,” said Lana Kandalaft, PharmD, MTR, PhD, Assistant Professor and Director of Clinical Development and Operations at the Ovarian Cancer Research Center in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, PA.

The two independent consecutive phase 1 studies enrolled 31 patients with recurrent progressive stage 3 and 4 ovarian cancer with available tumor lysate from secondary debulking surgery, which they used to create a personalized vaccine for each patient.

The first six patients “underwent priming with intravenous bevacizumab and oral metronomic cyclophosphamide followed by vaccination with an autologous dendritic cell preparation pulsed with freeze-thaw autologous tumor lysate,” Dr. Kandalaft reported. The other 25 patients were assigned to an enhanced vaccine with an optimized platform developed at the Penn Ovarian Cancer Research Center in which “autologous dendritic cells were loaded with HOCl-oxidized autologous tumor lysate administered intra-nodally every 2 weeks in combination with intravenous bevacizumab,” she added.

“Both studies were followed by lymphodepletion and transfer of autologous vaccine-primed, ex vivo CD3/CD28-co-stimulated peripheral blood T-cells, in combination with antiangiogenesis therapy and vaccination.”

Vaccination was found to elicit tumor-specific T cell responses against various ovarian tumor antigens. “Following lymphodepletion, adoptive transfer of vaccine-primed T-cells was well tolerated and resulted in durable reduction of T-regulatory cells and restoration of vaccine-induced antitumor immunity in patients who experienced clinical benefit,” Dr. Kandalaft reported.

Of the 31 patients, 20 (66%) showed clinical benefit after being treated with the vaccine; three had a partial response and 17 had stable disease, including six patients who entered the study with no evidence of disease. Patients who remain disease-free include one at 45 months, one at 36 months; two with no evidence of disease at 1 year, and one at 6 to 7 months, she reported.

A total of 11 patients who responded to the vaccine but still had residual disease moved to step 2, adoptive T-cell therapy, which amplified the anti-tumor immune response. Of these patients, seven (75%) had a clinical benefit; one a complete response.

“We offer patients with ovarian cancer a potential therapy with minor side effects and a good quality of life,” Dr. Kandalaft said. The team continues to work to improve the vaccine platform to further enhance its efficacy, and the trial remains open to accrual to test new combinatorial strategies.

This study was funded by a National Cancer Institute Ovarian Specialized Program of Research Excellence grant, the National Institutes of Health and the Ovarian Cancer Immunotherapy Initiative.

Abstract

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