A personalized vaccine targeted to a patient’s own tumor cells yielded promising results in patients with recurrent advanced ovarian cancer, a Phase 1 pilot trial shows.
The vaccine was safe, capable of triggering a broad anti-tumor immune response, and significantly delayed disease progression in patients responding to the therapy.
The study “Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer” was published in the journal Science Translational Medicine.
The new immunotherapy is a personalized vaccine made from the patient’s own immune cells, namely dendritic cells, stimulated to target a tumor.
Most cancer vaccines are designed to attack a specific known target, for instance, a receptor at the cell surface that is frequently present in that type of tumor. But even for the same type of cancer, each patient’s tumor has a unique set of mutations and looks different to the immune system.
The new approach followed by the researchers creates a vaccine personalized for each patient, taking advantage of the body’s natural anti-tumor immunity brought about by T-cells.
From each patient, researchers collected white blood cells that then were grown in the laboratory into a large population of dendritic cells, a specific type of immune cells. These cells normally take up and break down foreign material, including infectious agents or tumors, re-exposing pieces of it — called antigens — to immune cells.
The display of antigens by dendritic cells is crucial for triggering T-cells to specifically attack the foreign invader, in this case the tumor.
In the study, the patients’ dendritic cells derived in the laboratory were put in contact with extracts of the patient’s tumor. Then, dendritic cell activity was enhanced with compounds that trigger immune activation and injected into the patient’s lymph nodes.
This created a whole-tumor vaccine intended to promote a broader and more effective response to each individual tumor.
“The idea is to mobilize an immune response that will target the tumor very broadly, hitting a variety of markers including some that would be found only on that particular tumor,” Janos L. Tanyi, MD, PhD, study lead author said in a press release. Tanyi is an assistant professor of obstetrics and gynecology at the University of Pennsylvania School of Medicine.
The study was a single-center Phase 1 clinical trial (NCT01132014), evaluating the safety and activity of the vaccine OC-DC – dendritic cells pulsed with oxidized autologous whole-tumor cell lysate — alone or in combination with the drugs Avastin (bevacizumab) and cyclophosphamide.
The most recent study enrolled 25 patients with recurrent advanced ovarian cancer, most of whom had received several prior lines of chemotherapy and who never received immunotherapy before.
Patients received five doses of vaccines every three weeks and continued on a monthly maintenance regimen until the disease progressed or the vaccine supply was gone.
Five patients received only the OC-DC vaccine, a second group of 10 patients received OC-DC vaccine plus intravenous Avastin (a drug that targets the tumor’s blood vessels) and a third group of 10 patients received intravenous cyclophosphamide followed by OC-DC vaccine plus intravenous Avastin.
All vaccine injections were well-tolerated, and most vaccine-related toxicities were transient and low. The combination with Avastin and chemotherapy also was tolerated well.
The vaccine induced a positive anti-tumor T-cell response in 11 of the 22 patients evaluated. Those responding to the vaccine lived for significantly longer periods without cancer worsening, compared to those who did not respond.
Eight of the 11 vaccine responders achieved cancer remission that lasted longer than the prior remission event, whereas none of the non-responders experienced the same degree of remission.
Importantly, the two-year overall survival rates of the responder patients was 100 percent; in non-responders it was 25 percent.
One patient receiving the vaccine, who had two relapses after prior chemotherapy treatments, remained in remission for five additional years after discontinuing the vaccine.
Overall, combination with cyclophosphamide heightened the vaccine’s effectiveness, leading to a significantly higher proportion of vaccine responders (eight of 10) compared to those not treated with cyclophosphamide (three of 12).
Vaccine plus cyclophosphamide also significantly prolonged survival at two years in a larger number of patients, when compared with vaccine plus Avastin.
Another promising finding was that the vaccine-induced T-cells could recognize unique targets on their tumors, indicating a stronger capacity for attacking the patient’s tumor specifically without killing healthy cells.
Researchers expect to explore and improve the vaccine in future studies. “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 Tanyi.
Although these personalized vaccines might be difficult to produce, “these pilot clinical observations along with our biological observations provide encouraging data for the pursuit of DC [dendritic cell] vaccines,” the researchers wrote.
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