In collaboration with the Department of Oncology UNIL-CHUV, the Ludwig Lausanne Branch has launched two clinical trials of novel cancer vaccines, with a third nearing regulatory approval by the local Swissmedic authorities. All three trials are evaluating dendritic cell (DC) vaccines, in which dendritic cells obtained from a patient are cultured, loaded with neoantigens—the novel antigens, specific to each patient’s cancer, that are generated by random mutations across the cancer genome—and then reinfused into patients for therapy. Dendritic cells then present the neoantigens to T cells, activating a highly targeted immune response against each patient’s cancer.
The first trial, which started last year, is named PEP-DC and will examine the ability of personalized dendritic cell vaccines to prevent the recurrence of pancreatic cancer. The phase 1b trial will enroll 10-12 patients who have undergone surgery and have either no detectable cancer or a low burden of disease. They will all be treated with standard of care therapy plus immunotherapy and the personalized DC vaccine. A pair of patients have already received their personalized vaccines. The second trial, named LUNGVAC, started in December 2021. It is expected to ultimately enroll 16 patients with advanced or metastatic non-small cell lung cancer who will receive standard of care along with the personalized DC vaccine. The objective is to determine whether the vaccine amplifies responses to therapy. One patient enrolled in LUNGVAC has already received the personalized DC vaccine.
The trial now in the final stages of review by Swissmedic is a phase 1/2 trial of two types of DC vaccines for patients with high-grade serous ovarian carcinoma. It will enroll 16 patients, half of whom will receive the personalized peptide DC vaccine, in which neoantigenic peptides identified in each patient’s cancer are used to pulse dendritic cells to prepare the vaccine. The other half will receive a vaccine prepared with dendritic cells that have been pulsed with whole tumor extracts obtained from the patient and processed using a method under development at Ludwig Lausanne to improve vaccine immunogenicity. They will also receive the PEP-DC vaccine. Both cohorts will additionally receive maintenance treatment of low-dose chemotherapy after being treated with the initial standard of care therapy.
Ludwig Lausanne’s Lana Kandalaft, who also leads the CHUV’s department of oncology’s Center for Experimental Therapeutics, is overseeing the clinical trial program. The vaccine preparation and the immunologic analysis of patient responses is conducted by Ludwig Lausanne’s Human integrated Tumor Immunology Discovery engine (Hi-TIDe), led by Branch Director George Coukos. The immunopeptidomics group of the Hi-TIDe, led by Michal Bassani-Sternberg, is responsible for identifying and prioritizing neoantigens for personalized vaccine preparation, while the T cell discovery group, led by Alexandre Harari, will be monitoring the immune responses elicited by vaccination in the three trials.
This article appeared in the May 2022 issue of Ludwig Link. Click here to download a copy (PDF, 2MB).