Researchers have found that all nine participants in a clinical trial focusing on stage III or IV clear cell renal cell carcinoma (a type of kidney cancer) achieved a successful anti-cancer immune response after receiving a personalized cancer vaccine.
Scientists at Dana-Farber Cancer Institute have revealed that every one of the nine patients enrolled in a clinical trial for stage III or IV clear cell renal cell carcinoma generated a positive anti-cancer immune reaction following the introduction of a personalized cancer vaccine. These vaccines were given post-surgery, aimed at helping the immune system recognize and eliminate any leftover tumor cells. As of the last data review (with a median follow-up of 34.7 months), all patients remained free of cancer.
The findings from this phase 1 trial were unveiled today in Nature.
“We are thrilled about these results, which indicate a strong response in all nine kidney cancer patients,” stated co-senior author and co-principal investigator Toni Choueiri, MD, the Director of the Lank Center for Genitourinary Cancer at Dana-Farber.
Co-senior author Catherine Wu, MD, chief of the Division of Stem Cell Transplantation and Cellular Therapies at Dana-Farber and an associate at the Broad Institute, who played a crucial role in developing the NeoVax vaccine technology for this study, expressed, “This outcome is a result of close collaboration with our NeoVax team and colleagues from the Broad Institute and the Lank Center at Dana-Farber. We are elated to share these findings.”
Other co-senior authors include Patrick Ott, MD, PhD, director of the Center for Cancer Vaccines at Dana-Farber, and Derin Keskin, PhD, an immunologist at the same center. The study’s lead author is David A. Braun, MD, PhD, who previously worked at Dana-Farber and Harvard Medical School and currently is a medical oncologist and physician-scientist at Yale Cancer Center and Yale School of Medicine.
The conventional approach for treating patients with stage III or IV clear cell renal cell carcinoma entails the surgical removal of the tumor. This is often followed by immunotherapy using pembrolizumab, an immune checkpoint inhibitor that helps trigger an immune response to minimize the chances of cancer recurrence. Unfortunately, about two-thirds of patients still face recurrence and have limited treatment options.
“Individuals diagnosed with stage III or IV kidney cancer have a pronounced risk of recurrence,” Choueiri noted. “Current methods to mitigate that risk are not ideal, and we are persistently searching for improved solutions.”
In this investigator-initiated trial, Choueiri and Braun administered a personalized cancer vaccine to nine patients post-surgery. Five of those patients also received the vaccine alongside ipilimumab.
The personalized vaccines are crafted to identify each patient’s unique cancer using tumor tissue removed during surgery as a reference. The research team analyzes the tumor cells for distinct molecular characteristics that set them apart from healthy cells. These distinguishing features, called neoantigens, are small fragments of mutated proteins found in cancer cells but not in any normal cells.
Using predictive algorithms, the team selects which neoantigens to incorporate into the vaccine based on their potential to elicit an immune response. The vaccine is then produced and provided to the patient through an initial series of doses followed by two booster shots.
“This method stands apart from previous vaccine efforts in kidney cancer,” Braun explained. “We target elements that are exclusive to the cancer and distinct from any normal tissues, allowing the immune system to be finely directed towards the cancer. We have identified which specific cancer targets are most vulnerable to immune attack and shown that this strategy can produce lasting immune responses, enabling the immune system to identify cancer effectively. We believe this research establishes a framework for the creation of neoantigen vaccines for kidney cancer.”
While some patients noted local reactions at the injection sites and others experienced mild flu-like symptoms, no severe side effects were reported.
“The neoantigens that this vaccine focuses on aid in directing immune responses towards cancerous cells, aiming to enhance effectiveness while minimizing unwanted immune reactions,” said Choueiri.
When this research began eight years ago, it was uncertain if such an approach would be viable for kidney cancer, which had previously shown promise primarily in melanoma, a type of skin cancer known for having a higher mutation rate and thus more neoantigens.
Kidney cancer, on the other hand, has fewer mutations and therefore fewer elements to create vaccines from. The research team aimed to gather substantial information from this preliminary trial on how the vaccine impacts immune responses to tumors.
Through various analyses, they discovered that the vaccine sparked an immune response within three weeks, with a mean increase of 166-fold in vaccine-induced T cells, which persisted for up to three years. Additionally, laboratory studies indicated that these vaccine-induced T cells were effective against the patient’s tumor cells.
“We witnessed a quick, significant, and lasting growth of new T cell clones linked to the vaccine,” Ott said. “These findings reinforce the possibility of developing a highly immunogenic personalized neoantigen vaccine even in tumors with a lower mutation burden and are promising, but larger studies are necessary to fully evaluate the clinical effectiveness of this strategy.”
Further clinical trials involving more patients are essential to validate the effectiveness of the vaccine and explore its broader potential. A current multicenter international randomized study will also administer a similarly designed neoantigen-targeting personalized cancer vaccine in combination with immunotherapy pembrolizumab (NCT06307431). Choueiri is serving as the co-chair of its Scientific Advisory Committee.
