Cancer vaccine and adoptive T-cell therapy could benefit patients with advanced ovarian cancer- study

Combining adoptive T-cell therapy (ACT) with a personalised cancer vaccine could benefit patients with late-stage, drug-resistant ovarian cancer, a Ludwig Cancer Research study has shown.

Researchers led by Ludwig Lausanne’s Sara Bobisse, Alexandre Harari, Lana Kandalaft and director George Coukos analysed responses to the combination therapy of 18 patients with advanced ovarian cancer who had previously participated in a clinical trial evaluating a therapeutic regimen that incorporated the personalised cancer vaccine.

In the current study, patients received an infusion of their own vaccine-primed, circulating immune cells (specifically, T-cells), followed by multiple periodic doses of their personalised vaccines.

The researchers reported that combining the personalised cancer vaccine with T-cell therapy, a type of immunotherapy that makes a patient’s immune cells fight cancer, yielded control of the disease within three months in 12 of 17 patients.

The treatment was also found to be safe and relatively well tolerated.

“This treatment could not eliminate tumours, but it did provide considerable benefit to many of the patients, who had all undergone extensive treatment prior to enrolling in the trial and were in the late stages of the disease,” said Kandalaft.

Ovarian cancer is the sixth most common cancer in the UK, with around 7,500 new cases every year.

Like many other malignancies, ovarian cancer has so far proved largely resistant to immunotherapies, most of which harness killer T-cells, which destroy sick and infected cells.

Ovarian cancer cells do, however, express neoantigens, which are randomly mutated proteins that can activate anti-tumour T-cell responses.

Multiple approaches are today being developed at Ludwig Lausanne and elsewhere to target neoantigens for cancer immunotherapy. The personalised dendritic cell vaccine, developed over the past dozen years under the leadership of Kandalaft and Coukos, is one of them.

To make the vaccine, researchers first coax precursor immune cells isolated from patients to turn into dendritic cells, which present cancer antigens to killer T-cells to direct and activate their anti-tumour responses.

These dendritic cells are then expanded in culture and pulsed with an extract of cancer cells from a patient’s tumour that is chemically treated to improve uptake and processing of antigens by the cultured immune cells.

The vaccine is then injected into its corresponding patient’s lymph nodes, the anatomical site where dendritic cells activate anti-tumour T-cells.

In the current study, patients received chemotherapy followed by ACT using vaccine-primed T-cells that were expanded in culture in the presence of stimulatory immune factors. The ACT was followed by several cycles of vaccination.

“We were very happy that we could demonstrate how the combination therapy improved anti-tumour immune responses, and that those changes correlated to patient benefit,” said Ludwig Lausanne’s Bobisse.

“Most notably, we could show that T-cells targeting the neoantigens were reinvigorated by the combination therapy and correlated with positive responses to the therapy.”

Further, DNA sequences encoding neoantigens targeted by the T-cells were found at higher levels in circulating tumour DNA, suggesting they had invited the destruction of tumour cells.

Coukos, the director of the University Hospital of Lausanne Switzerland’s department of oncology, said: “This study illustrates how rational approaches to the design of immunotherapies can help overcome the barriers to immune responses that are erected by a variety of cancers, not least ovarian cancer.

“It has also taught us valuable lessons that we will be sure to apply to improve the efficacy of personalised cancer immunotherapies we’re developing here at Ludwig Lausanne.”