Innovative Combination Therapy Shows Promise for Late-Stage Ovarian Cancer

Combining adoptive T-cell therapy (ACT) with a personalized cancer vaccine has been shown to benefit patients with late-stage, drug-resistant ovarian cancer, according to research published in Nature Cancer.¹

The study was led by scientists at the Lausanne Branch of the Ludwig Institute for Cancer Research and used a cancer vaccine that is currently under development at the institute.

The study enrolled 19 patients with advanced ovarian cancer who had previously participated in a clinical trial assessing a therapeutic regimen incorporating the personalized cancer vaccine. In the current study, patients received an infusion of their own vaccine-primed T cells, followed by multiple periodic doses of their personalized vaccines.

This regimen combined the dendritic cell vaccine with bevacizumab, a standard ovarian cancer therapy targeting VEGF-A, a factor secreted by cancer cells that promotes blood vessel formation and hampers killer T cell entry into tumors. Patients also received low doses of chemotherapy to clear existing T cells from lymph nodes, making room for the newly infused T cells. This chemotherapy, including cyclophosphamide, also suppressed regulatory T cells, which inhibit killer T cell responses.

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The findings indicate that combining the personalized cancer vaccine with ACT resulted in disease control within 3 months for 12 of the 17 patients who completed the entire combination treatment. The combination treatment was found to be safe and generally well-tolerated.

“This treatment could not eliminate tumors, but it did provide considerable benefit to many of the patients, who had all undergone extensive treatment prior to enrolling in the trial and were in the late stages of the disease,” said Lana Kandalaft, PharmD, PhD, associate professor at the University of Lausanne and director of the Center of Experimental Therapeutics at the Lausanne University Hospital, in a news release.²

While not a double-blind, placebo-controlled trial, the study's results suggest significant benefits from the combination therapy. The median overall survival time for patients who completed the regimen was 14.2 months, compared with a median historical survival of 6 months or less for comparable patients receiving fourth- and fifth-line chemotherapy.

Ovarian cancer has historically demonstrated resistance to immunotherapies, which primarily rely on activating killer T cells to destroy cancer cells. However, ovarian cancer cells do express neoantigens, which are randomly mutated proteins that can activate anti-tumor T-cell responses.

Researchers at Ludwig Institute for Cancer Research and elsewhere are exploring various approaches to target these neoantigens for cancer immunotherapy, and the personalized dendritic cell vaccine developed over the past 12 years under the leadership of Kandalaft and George Coukos, MD, PhD, director of the Department of Oncology at the Lausanne University Hospital, has been deemed a promising one.

The process involves coaxing precursor immune cells from patients to transform into dendritic cells, which then present cancer antigens to killer T cells, activating their anti-tumor responses. These dendritic cells are then cultured and exposed to an extract of cancer cells from the patient's tumor, chemically treated to enhance antigen uptake and processing. The vaccine is then injected into the patient's lymph nodes, where dendritic cells activate anti-tumor T cells.

“This study illustrates how rational approaches to the design of immunotherapies can help overcome the barriers to immune responses that are erected by a variety of cancers, not least ovarian cancer,” said Coukos. “It has also taught us valuable lessons that we will be sure to apply to improve the efficacy of personalized cancer immunotherapies we’re developing here at Ludwig Lausanne.”

References

1. Bobisse S, Bianchi V, Tanyi JL, et al. A phase 1 trial of adoptive transfer of vaccine-primed autologous circulating T cells in ovarian cancer. Nat Cancer. Published online September 21, 2023. doi:10.1038/s43018-023-00623-x
2. Combination of cancer vaccine and T cell therapy benefits patients with advanced ovarian cancer. News release. Ludwig Cancer Research. September 21, 2023. Accessed September 22, 2023. https://www.newswise.com/articles/combination-of-cancer-vaccine-and-t-cell-therapy-benefits-patients-with-advanced-ovarian-cancer