Kidney Cancer Vaccine Shows Promise in Early Trial

While the results remain to be replicated in larger studies, the researchers caution, these early findings raise hope that an anti-tumor vaccine is feasible for treatment of patients with kidney cancer at high risk of recurrence.

“We’re very excited about these results, which show such a positive response in all nine patients with kidney cancer,” says co-senior author and co-principal investigator Toni Choueiri, the HMS Jerome and Nancy Kohlberg Chair and Professor of Medicine and director of the Lank Center for Genitourinary Cancer at Dana-Farber.

The vaccines, designed to train the body’s immune system to recognize and destroy cancer, were administered after surgery to eliminate any remaining tumor cells. At the time researchers paused data collection, all nine patients had remained cancer free for a median of 40 months after surgery.

“This study was the result of a close partnership between our NeoVax team, our colleagues at the Broad Institute of MIT and Harvard, and our colleagues at the Lank Center for Genitourinary Cancer at Dana-Farber,” said co-senior author Catherine Wu, HMS professor of medicine and chief of the Division of Stem Cell Transplantation and Cellular Therapies at Dana-Farber and an institute member at the Broad, who developed the NeoVax vaccine technology used to create the personalized cancer vaccines for this trial. “We are thrilled to report these results.”

Clear cell renal cell carcinoma is the most common form of kidney cancer. Standard treatment for patients with stage III and IV of the disease is surgery to remove the tumor. Surgery can be followed by immunotherapy with a drug called pembrolizumab, an immune checkpoint inhibitor. Pembrolizumab induces an immune response that reduces the risk of the cancer relapse. However, about two-thirds of patients can still experience cancer recurrence that leaves them with limited treatment options.

“Patients with stage III or IV kidney cancer are at high risk of recurrence,” says Choueiri. “The tools we have to lower that risk are not perfect and we are relentlessly looking for more.”

In the current study, the researchers treated all nine patients with the personalized cancer vaccine after surgery. Five of them also received the drug ipilimumab, a form of cancer immunotherapy.

The vaccines were individualized to each patient using genetic material from their tumor as a way to teach the immune system to spot and destroy the cancerous cells. To do so, the scientists extracted tiny fragments of mutant proteins — called neoantigens — from each patient’s kidney tumor. These neoantigens are a tumor’s molecular signature — highly specific to the cancer and not found in any other cells in the body.

The team also used predictive algorithms to gauge which of the neoantigens were the most likely to induce an immune response. The vaccine was then made and administered to the patient in a series of initial doses followed by two boosters.

Some patients experienced minor local reactions at the injection site, and some developed flu-like symptoms. There were no other, more serious side effects.

“The neoantigens targeted by this vaccine help steer immune responses toward cancer cells, with the goal to improve on-target efficacy and reduce off-target immune toxicity,” Choueiri said.

When the team initiated this study eight years ago, it wasn’t clear whether this approach could work in kidney cancer. The approach had already shown promise in melanoma, a deadly form of skin cancer that has many more mutations and therefore many possible neoantigens.

But kidney cancer is a disease with fewer mutations, and therefore fewer targets to use in the vaccine. It was important for the investigators to learn as much as possible from this early-phase study about how the vaccine influences an immune response to the tumor.

Through a series of analyses, the team found that the vaccine induced an immune response within three weeks, the number of vaccine-induced T cells increased by 166-fold, on average, and these protective T cells remained in the body at high levels for up to three years. Laboratory experiments in human kidney tumor cells also showed that the vaccine-induced T cells were active against the patient’s own tumor cells.

“We observed a rapid, substantial, and durable expansion of new T-cell clones related to the vaccine,” said Patrick Ott, HMS associate professor and clinical director of the Melanoma Center and Medical Oncology at Dana-Farber. “These results support the feasibility of creating a highly immunogenic personalized neoantigen vaccine in a lower-mutation-burden tumor and are encouraging, though larger-scale studies will be required to fully understand the clinical efficacy of this approach.”

An ongoing multicenter international randomized study using a similar neoantigen-targeting personalized cancer vaccine will be administered in combination with immunotherapy pembrolizumab (NCT06307431). Choueiri serves as the co-chair of its Scientific Advisory Committee.

Adapted from a Dana-Farber press release.