A personalized cancer vaccine developed with the help of a bioengineering platform at Mount Sinai Hospital in New York, USA, raised no safety concerns and showed potential benefit in patients with different types of cancers, including lung cancers and bladder, which have a high risk of recurrence, according to results from an investigator-initiated phase I clinical trial presented during the virtual annual meeting of the American Association for Cancer Research (AACR), held from April 10 to 15.

While immunotherapy has revolutionized cancer treatment, the vast majority of patients do not experience a significant clinical response to such treatments,” said study author Dr. Thomas Marron, deputy director of early-phase and immunotherapy trials at the Tisch Cancer Institute and Assistant Professor of Medicine (Hematology and Medical Oncology) at the Icahn School of Medicine at Mount Sinai. “Cancer vaccines typically combine tumor-specific targets that the immune system can learn to recognize and attack to prevent cancer recurrence. The vaccine also contains an adjuvant that primes the immune system to maximize effectiveness.

To generate the personalized cancer vaccine, Dr. Marron and colleagues sequenced tumor and germline DNA and tumor RNA from each patient. They also identified the specific target of the patient’s tumor to help predict whether the patient’s immune system would recognize the vaccine targets.
Mount Sinai’s bioengineering platform, called OpenVax, enables researchers to identify and prioritize immunogenic targets to synthesize and incorporate into a vaccine.
After any standard cancer treatment, such as surgery for solid tumors or bone marrow transplant for multiple myeloma, patients received 10 doses of the personalized vaccine over a six-month period.

The vaccine was administered with the immunostimulant, or adjuvant, poly-ICLC, which is “a synthetic, stabilized, double-stranded RNA capable of activating multiple innate immune receptors, making it the optimal adjuvant to induce immune responses against tumor neoantigens.” said study author Dr. Nina Bhardwaj, Director of the Immunotherapy Program and Ward-Coleman Chair in Cancer Research at the Tisch Cancer Institute at Mount Sinai.

Most of the experimental personalized cancer vaccines are given to patients with metastatic cancer, but previous research indicates that immunotherapies tend to be more effective in patients who have less spread of cancer,” said Dr. Bhardwaj. “Therefore, we have developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplantation in multiple myeloma, when patients have minimal residual disease, typically microscopic. Our results demonstrate that the OpenVax bioengineering platform is a viable option for generating a safe, personalized cancer vaccine that could be used to treat a variety of tumor types.

Before the vaccine, trial participants had a statistically high chance of disease recurrence. Thirteen patients received the Mount Sinai team’s vaccine: 10 had solid tumor diagnoses and 3 had multiple myeloma.
After a median follow-up of 880 days, four patients still had no evidence of cancer, four were receiving subsequent lines of therapy, four had died, and one decided not to continue with the trial. The vaccine was well tolerated and approximately one third of patients developed mild injection site reactions.
The main goal of a phase 1 trial is to determine the safety of an experimental treatment, which was achieved in this trial. The researchers also saw early potential benefits of the vaccine after blood tests from one of the patients showed an immune response to the vaccine, and two other patients had a robust response to immunotherapy afterward, results that are normal after have been exposed to a cancer vaccine.
Since the completion of this trial, Mount Sinai has opened or plans to open an additional five Phase 1 trials testing OpenVax with other therapies in cancers including glioblastoma, bladder cancer, prostate cancer, and myeloproliferative neoplasms (a blood cancer). This study was sponsored by the Parker Institute for Cancer Immunotherapy and the Tisch Cancer Institute.