Safe, personalized cancer vaccine shows promise in early trials

NEW YORK — A personalized cancer vaccine may sound more like fiction than reality to some. However, researchers from Mount Sinai Hospital report they’ve developed just that with the help of a computational platform. Even better, these personalized vaccines — treating forms of the disease including lung and bladder cancer — appear safe for use and beneficial for patients at high risk of recurrence. These findings come from the initial results of a phase-1 clinical trial involving the vaccines.

“While immunotherapy has revolutionized the treatment of cancer, the vast majority of patients do not experience a significant clinical response with such treatments,” says study author Thomas Marron, MD, PhD, Assistant Director for Early Phase and Immunotherapy Trials at The Tisch Cancer Institute and Assistant Professor of Medicine at the Icahn School of Medicine at Mount Sinai, in a media release. “Cancer vaccines, which typically combine tumor-specific targets that the immune system can learn to recognize and attack to prevent recurrence of cancer. The vaccine also contains an adjuvant that primes the immune system to maximize the efficacy.”

Using tumor DNA to make better cancer drugs

Researchers sequenced each individual patient’s tumor and germline DNA and tumor RNA to create a personalized vaccine. Moreover, the team noted each patient’s tumor-specific target. This helped give scientists a better idea of whether or not the patient’s immune system would recognize the vaccine’s targets.

Then, Mount Sinai’s computational pipeline, OpenVax, helped researchers identify and prioritize immunogenic targets to synthesize and add to each vaccine.

In the six months following any standard cancer treatments, each participating cancer patient received 10 doses of the personalized vaccine. Doctors administered the vaccines via the immunostimulant (adjuvant, poly-ICLC). Co-study author Nina Bhardwaj, MD, PhD, describes this as “a synthetic, stabilized, double-stranded RNA capable of activating multiple innate immune receptors, making it the optimal adjuvant for inducing immune responses against tumor neoantigens.”

“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” Dr. Bhardwaj explains. “We have therefore developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in multiple myeloma, when patients have minimal–typically microscopic–residual disease. Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types.”

Scientists reveal a promising first step

Before taking the vaccine, each patient in the trial had a “statistically-high” chance of cancer recurrence. Among the 13 patients receiving a personalized vaccine, 10 had solid tumor diagnoses and three had multiple myeloma to start.

After an average of 880 days, four of those patients showed no signs of cancer. Another four continued receiving more treatments and four passed away. The final volunteer decided to stop participating in the study. Generally, study authors report the group tolerated the treatments well. Although, about one-third of patients did show minor injection-site reactions.

The purpose of a phase 1 trial is only to establish the safety of a new treatment. So, in that sense, phase 1 was largely a success. Additionally, one patient showed a tangible immune response to the vaccine. Two others displayed a “robust” reaction to subsequent immunotherapy treatments.

The Mount Sinai team presented their findings at the American Association for Cancer Research (AACR) Annual Meeting 2021.

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