Personalized Cancer Vaccine Looks Promising in Early Study
Twenty-five platinum-pretreated, immunotherapy-naïve patients with recurrent advanced epithelial ovarian cancer were enrolled in the trial
A cancer vaccine developed to target a patient's own tumor cells has demonstrated promising results in a new study published in the journal Science Translational Medicine.
Researchers at the Perelman School of Medicine and the Abramson Cancer Center, at the University of Pennsylvania, developed the vaccine using dendritic cells (DCs) derived from each patient's own peripheral blood mononuclear cells. These dendritic cells were then exposed to the patient's tumor cells, activated with interferon gamma, and injected into the patient's lymph nodes.
The researchers enrolled 25 platinum-pretreated, immunotherapy-naïve patients with recurrent advanced epithelial ovarian cancer (EOC) for the trial. The novel vaccine of tumor-exposed DCs (using autologous oxidized whole-tumor cell lysate pulsed on autologous 5-day-old DCs), was administered every 3 weeks. The number of doses for patients ranged from 2 to 28 (median=9).
Results showed that vaccine-reactive T cells were readily detectable in on-vaccination peripheral blood mononuclear cells (PBMCs), but were significantly lower or undetectable in prevaccination PBMCs (P=0.001). Patients whose postimmunization T cells recognized autologous tumor cells or DC-presented tumor antigen, demonstrated significantly longer progression-free survival (PFS) on immunotherapy than those whose T cells did not respond to either.
The 2-year overall survival (OS) rate for nonresponders was 25%, compared to 100% in the responder group. To test whether the survival results were related to the vaccine, researchers stimulated T cells from each patient collected before or after the immunotherapy, using staphylococcal enterotoxin B (SEB). Results showed a very similar T cell response to SEB between vaccine responders and nonresponders at baseline and after immunotherapy, which the researchers write, suggests "that perhaps the therapy changed the natural course of the disease".
A 46-year old patient who started the trial with stage 4 ovarian cancer and had had 5 previous courses of chemotherapy remained disease-free for 5 years after completing treatment with her personalized vaccine. She had received 28 doses of vaccine over a 2-year period.
“This vaccine appears to be safe for patients, and elicits a broad anti-tumor immunity – we think it warrants further testing in larger clinical trials,” said lead author Janos L. Tanyi, MD, assistant professor of obstetrics and gynecology at Penn Medicine.
For more information visit Sciencemag.org.