A Phase I trial of a neoantigen vaccine to treat advanced kidney cancer at Dana-Farber Cancer Institute showed all patients remained cancer free at a median of 35 months follow up.
As reported in Nature, the vaccine was personalized to the nine patients in the trial depending on the genetics and tissue profile of their individual tumors.
The patients all had either stage III or IV kidney cancer and were operated on to remove the tumors before being treated with the vaccine. Five patients also had supplementary treatment with the checkpoint inhibitor ipilimumab. The tumor tissue removed during surgery was used to personalize the vaccine to each patient.
“We’re very excited about these results, which show such a positive response in all nine patients with kidney cancer,” said co-lead author and co-principal investigator Toni Choueiri, director of the Lank Center for Genitourinary Cancer at Dana-Farber, in a press statement.
The second co-lead author Catherine Wu, MD, is chief of the Division of Stem Cell Transplantation and Cellular Therapies at Dana-Farber. Wu developed the NeoVax technology used in the trial and won the Sjöberg Prize last February in recognition of her work on developing personalized cancer vaccines.
Surgery is currently the standard treatment for advanced renal cell carcinoma, which can then be followed by immunotherapy with a checkpoint inhibitor like pembrolizumab to try and prevent recurrence.
While this is highly effective in about a third of patients, two thirds have recurrence after surgery meaning that additional therapeutic options are needed.
The cancer vaccine tested in this study is designed to target neoantigens that are present on tumor cells but not seen in healthy tissue. The investigators test each patient’s tumor and then use computer algorithms to predict which neoantigens to add to the vaccine to provoke the most effective immune response.
“The neoantigens targeted by this vaccine help steer immune responses towards cancer cells, with the goal to improve on-target efficacy and reduce off-target immune toxicity,” says Choueiri. Indeed, the side effects in this trial were minimal and mostly consisted of injection site reactions and some flu-like symptoms.
Of the nine patients included in this study, all generated a T cell response to the neoantigens in the vaccine and driver mutations in the tumors. Anti-tumor T cell reactivity was detected in seven of the patients. The vaccine also appeared to increase the number of T cell clones being produced by the patients’ immune systems.
The vaccine will now move onto stage 2 testing to better assess its efficacy and to trial how effective combining this type of vaccine treatment with checkpoint inhibitor therapy is.