A recent research study conducted by Ludwig Cancer Research has revealed promising outcomes when combining adoptive T cell therapy (ACT) with a cutting-edge, individualized cancer vaccine currently in development at the Lausanne Branch of the Ludwig Institute for Cancer Research. The team, led by Ludwig Lausanne’s Sara Bobisse, Alexandre Harari, Lana Kandalaft, and Director George Coukos, examined the responses of 18 patients with advanced ovarian cancer who had previously participated in a clinical trial featuring the personalized cancer vaccine.
In this study, which also involved collaboration with researchers at the University of Pennsylvania, patients received infusions of their own vaccine-primed T cells, followed by periodic doses of their personalized vaccines. The results, reported in Nature Cancer, demonstrated that the combination of the personalized cancer vaccine with ACT led to disease control within three months for 12 out of 17 patients. Importantly, the treatment was safe and well-tolerated.
While this treatment did not completely eradicate tumors, it provided significant benefits to patients in advanced stages of the disease, who had undergone extensive prior treatments. Notably, the median overall survival time for patients who completed the regimen was 14.2 months, compared to the historical median survival of six months or less for similar patients undergoing fourth- and fifth-line chemotherapy.
Ovarian cancer, like many other types of cancer, has been largely resistant to immunotherapies. However, the presence of neoantigens—randomly mutated proteins that can activate anti-tumor T cell responses—in ovarian cancer cells offers hope for immunotherapy approaches. The personalized dendritic cell vaccine, developed over the past several years under the guidance of Kandalaft and Coukos, is one such approach.
To create the vaccine, researchers coax precursor immune cells from patients into dendritic cells, which present cancer antigens to killer T cells to activate their anti-tumor responses. These dendritic cells are then expanded in culture and pulsed with cancer cell extracts, enhancing antigen uptake and processing by the cultured immune cells. The vaccine is subsequently injected into the corresponding patient’s lymph nodes, where dendritic cells activate anti-tumor T cells.
Patients in the trial received a promising therapeutic regimen, involving the dendritic cell vaccine along with bevacizumab, a standard ovarian cancer therapy. Additionally, patients received low-dose chemotherapy to clear existing T cells from lymph nodes, making room for the newly infused T cells, and to suppress regulatory T cells, which inhibit killer T cell responses.
In the current study, patients received chemotherapy followed by ACT using vaccine-primed T cells expanded in culture with immune stimulants. This was followed by multiple cycles of vaccination. Encouragingly, the combination therapy enhanced anti-tumor immune responses, correlating with positive patient outcomes. T cells targeting the neoantigens were reinvigorated by the combination therapy and associated with positive responses to treatment.
Furthermore, DNA sequences encoding the targeted neoantigens were found at higher levels in circulating tumor DNA, suggesting that they played a role in the destruction of tumor cells. This study underscores the potential of rational approaches to immunotherapy in overcoming immune response barriers posed by various cancers, including ovarian cancer, and provides valuable insights for improving personalized cancer immunotherapies.
Source: Ludwig Cancer Research
