Personalized Melanoma Vaccine Elicits Strong Immune Response

Results of a Dana-Farber Cancer Institute-initiated Phase I clinical trial for patients with melanoma show that an updated formula and delivery of the NeoVax personalized cancer vaccine called NeoVaxMI is safe, feasible and improves the vaccine-specific immune response compared to previous trials of the platform.

NeoVaxMI is a personalized neoantigen-targeted vaccine based on the NeoVax platform originally developed at Dana-Farber by the study’s senior-author Patrick Ott, MD, PhD, clinical director of the Melanoma Disease Center at Dana-Farber and Catherine Wu, MD, chief of the division of stem cell transplantation and cellular therapies, who is also a senior author on the paper. NeoVax includes personalized neoantigens, which are protein fragments that appear on an individual patient’s cancer cells and not on normal cells, plus an immunostimulant called poly-ICLC. NeoVaxMI adds another immune-boosting compound called Montadine to the mix.

The trial enrolled patients with previously untreated advanced or high-risk melanoma with the goal to fully vaccinate all patients with NeoVaxMI and perform in-depth analysis of their immune responses. No formal clinical outcome assessments beyond the safety and feasibility of the vaccine were planned for the trial. 

Administration of NeoVaxMI in the trial included two additional immunotherapies. Patients received systemic nivolumab prior to, during and after the vaccine series. Systemic nivolumab reduces immune suppression and is standard of care therapy for patients with resected or advanced melanoma. They also received ipilimumab locally at the vaccination site during the vaccine series. The addition of subcutaneous delivery of ipilimumab was predicted to enhance the activation of T cells to respond to the antigens introduced by the vaccine.

Nine patients were fully vaccinated. To assess the magnitude of T cell responses induced by NeoVaxMI, the team isolated T cells from patient blood samples after vaccination and assessed their ability to recognize and respond to vaccine-specific neoantigens in a dish. They observed T cell responses to neoantigens in all nine patients and cytotoxic responses by special T cells called CD-8+ T cells in six of nine patients.

The investigators also examined skin biopsies taken from the vaccine and ipilimumab injection sites using leading edge single cell sequencing approaches. In these samples, they saw an increase in immune cells called macrophages after vaccination, suggesting NeoVaxMI primed the area to initiate immune activation in response to the vaccine.

The team also demonstrated that different sets of receptors expressed on the T cells emerged after vaccination compared to the standard treatment nivolumab. The number of types of distinct vaccine-specific T cells activated after vaccination exceeded the number produced after treatment with nivolumab, suggesting a potent vaccine-induced immune response. 

Based on tumor samples from four patients and using new technologies enabling definitive interrogation of individual (single) T cells, the team confirmed that the vaccine-induced T cells infiltrated tumors.

“These are exciting observations showing that this new formulation and delivery strategy improves the power of the vaccination,” says Dr. Ott. “The methods we used to measure the immune responses are rigorous and unique in the field in the setting of a clinical trial. Studies like this are important if we want to continue to improve personalized cancer vaccines.”

NeoVaxMI was well-tolerated and did not introduce new safety concerns. However, the study is limited by its small size and by the introduction of three new agents together, which makes it difficult to attribute observed improvements to specific changes to the vaccine.