Cancer researchers are one step closer to developing an effective vaccine to treat people with clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer among adults.
In an early-stage clinical trial led by the Dana-Farber Cancer Institute in Boston, a personalized vaccine prompted an anti-cancer immune response in all nine participants. These patients had been diagnosed with advanced disease and were given the vaccine after their tumors had been surgically removed. All remained cancer-free after a median follow-up period of just under three years. The trial results were published Feb. 5 in the journal Nature.
“Patients with Stage 3 or 4 kidney cancer are at high risk of recurrence,” Dr. Toni Choueiri, director of Dana-Farber’s Lank Center for Genitourinary Cancer, said in a news release about the research. “The tools we have to lower that risk are not perfect and we are relentlessly looking for more.”
Tumor removal is the current standard of late-stage ccRCC treatment. In 2021, the Food and Drug Administration approved Keytruda (pembrolizumab), an immunotherapy manufactured by Fortune 500 firm Merck, for post-surgical use in people with kidney cancer. While Keytruda may help lower a person’s risk of cancer recurrence, it doesn’t work for all patients.
What’s a personalized vaccine?
Trial researchers, in a sense, manipulated each patient’s cancer in an attempt to prevent it from coming back. That is, they fashioned personalized vaccines using the very fabric of the tumors that had been removed.
From the tumor tissue, researchers extracted neoantigens, which are bits of mutated proteins unique to cancer cells. Predictive algorithms helped the team gauge which neoantigens might elicit an immune response and should therefore be included in the vaccine. Dana-Farber has dubbed this biotechnology, which trains the immune system to destroy any remaining cancer cells, NeoVax.
Previous research has shown NeoVax to be potentially effective in treating melanoma. This form of skin cancer has more mutations than ccRCC, meaning it offers physician-scientists more neoantigens to draw from. That NeoVax appears promising in the treatment of kidney cancer is a win, researchers said.
“This approach is truly distinct from vaccine attempts in kidney cancer,” study coauthor Dr. David Braun, formerly of Dana-Farber and now a medical oncologist at Yale Cancer Center, said in the news release. “We pick targets that are unique to the cancer and different from any normal part of the body, so the immune system can be effectively ‘steered’ toward the cancer in a very specific way.
“We learned which specific targets in the cancer are most susceptible to immune attack and demonstrated that this approach can generate long-lasting immune responses, directing the immune system to recognize cancer. We believe this work can form a foundation for the development of neoantigen vaccines in kidney cancer.”
Braun and Choueiri administered personalized vaccines to the nine trial patients, five of whom also received Yervoy (ipilimumab), an immunotherapy made by Fortune 500 company Bristol-Myers Squibb. Within three weeks, the vaccine triggered a promising immune response.
“We observed a rapid, substantial, and durable expansion of new T-cell clones related to the vaccine,” Dr. Patrick Ott, director of Dana-Farber’s Center for Cancer Vaccines, said in the news release. T cells are a type of white blood cell critical to the immune system. Ott added that while the results are encouraging, “larger-scale studies will be required to fully understand the clinical efficacy of this approach.”
In the meantime, Choueiri is involved in a mid-stage Merck-led trial, in which nearly 300 patients with kidney cancer are being given Keytruda and either a placebo or a personalized immunization similar to NeoVax.
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