Personalized cancer vaccines now possible due to discovery of cancer frameshift neoantigens

By Samantha Black, PhD, ScienceBoard editor in chief

October 2, 2019 -- Researchers from Arizona State University's Biodesign Institute demonstrated experimental proof-of-concept that cancer mutations produce individual neoantigens, or newly formed antigens, and can be used for cancer vaccines. The new paper published in Scientific Reports on October 2, shows that neoantigens can be used to protect against cancer.

The research team lead by Stephen Albert Johnston, investigates universal vaccines to protect cancer. To do so, they discovered 200,000 cancer neoantigens some of which occurred repeated in various tumors, leading them to believe that it is possible to create one vaccine for all tumors.

In the current study, they examined mutations in over 50 cancer cell lines, and 85 tissue samples from Mayo Clinic Arizona, as well as blood from patients, form five different late-stage cancer types: lung, breast, brain, gastric, and pancreatic cancers.

The team believes that neoantigens could provide three levels of therapies with a cancer vaccine: a broad pan-cancer vaccine, a cancer-type specific vaccine, and personalized cancer vaccine. "In a cancer cell, it turns out that all levels of information transfer from DNA to RNA to protein become more error prone," said Johnston. "We proposed that these mistakes made in cancer cells may also be the source to make a cancer vaccine."

They identified a class of alterations termed "frameshift" or "splicing" errors, occur during RNA transcription. As cancer progresses and increases transcription inside the cell, the error build-up, overwhelming the regulatory process and erroneous proteins becoming exposed to the host immune system.

To quickly identify these frameshift mutations the research team designed an array representing all possible neoantigen peptides, containing nearly 400,000 frameshift peptides. The array was used to screen blood samples of cancer patients for the detection of antibody response. With the exception of glioblastoma, all cancers tested had significant antibody responses to the frameshift peptides in the array. The researchers also found that 69% to 80% of the frameshift peptides identified were unique to the individual but that 116-19% were shared within cancer type.

The top vaccine candidates were selected based on identification and screening experiments. Those candidates were then tested in several mouse studies.

The team also designed a gene gun to provided genetic immunization bu shooting gold nanoparticles containing the vaccine into the ears of mice, which were then challenged with cancer-causing cells. They found that the vaccines could provide a significant delay or prevent tumor growth or prevent progression of tumors in mice.

From this work, the scientists have created a "Top 100" peptide list for each of the cancers they tested. They conducted the first-in-kind dog cancer vaccine trial and hope to soon move into human clinical trials.

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