Fight tumour with tumour (and T cells)

Most ovarian cancer patients are diagnosed with late stage disease that is unresponsive to existing therapies. In a new study, researchers from the University of Pennsylvania School of Medicine show that a two-step personalised immunotherapy treatment – a dendritic cell vaccine using patients’ own tumour followed by adoptive T cell therapy – triggers anti-tumour immune responses in these patients.

Four of the six patients treated in the trial responded to the therapy, the investigators report in OncoImmunology.

“What we proved in this study is that this is a safe treatment strategy,” says co-first author Lana Kandalaft, PharmD, MTR, PhD, research assistant professor of Obstetrics and Gynaecology and director of clinical development in the Ovarian Cancer Research Centre. “It is a walk in the park for patients, especially compared to standard chemotherapies and surgical treatments for ovarian cancer – literally, some patients left the clinic and went for a walk in a nearby park after their treatment.”

Researchers treated six women with advanced ovarian cancer in a two-staged immunotherapy protocol, using a dendritic cell vaccine created from tissue in the patients’ own tumour, which was stored at time of surgery. All of these women’s cancers had progressed on standard of care chemotherapy.

Of the six patients who received the dendritic cell vaccine, four developed an anti-tumour immune response, indicating that the approach was working. One of those patients had no measurable disease at study entry because all of it had been successfully removed during surgery. She remains in remission today, 42 months following vaccine treatment. The other three who had an immune response to the vaccine still had residual disease and went on to the second segment of treatment.

The team harvested T cells from each of these three women, and then reintroduced them into each patient after she underwent a lymphodepleting chemotherapy regimen. The T cell transfer amplified the anti-tumour immune response.

Two of the women showed a restored immune response after the T cell transfer. One of the women continued to have stable disease, and the other had a complete response to the therapy.

The researchers say it is too early to say whether this type of therapy will be effective in a large number of ovarian cancer patients, but the results are promising. The two-step approach appears safe and well tolerated by the patients. Additionally, a correlation exists in both treatment steps between immune responses and clinical benefit, suggesting that it is, in fact, the immune response that is holding the disease in check.

Based on the encouraging results, the team has opened a larger trial. The new protocol uses an improved vaccine platform and an optimised adoptive T cell transfer protocol.

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