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Brain Cancer Vaccine Stops Tumor Growth In First Human Trial

Discussion in 'Oncology' started by Mahmoud Abudeif, Mar 30, 2021.

  1. Mahmoud Abudeif

    Mahmoud Abudeif Golden Member

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    A vaccine that targets a specific type of brain tumor has been tested on humans for the first time, with results indicating that it is both safe and effective for the treatment of cancer. The majority of patients enrolled in the trial developed an immune response to certain cancer-related proteins, with 82 percent of those who did so seeing a complete cessation in tumor growth for the next two years.

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    The vaccine was developed as a treatment for diffuse gliomas, which are spread throughout the brain and are therefore difficult to remove surgically, while standard treatments such as chemotherapy and radiotherapy often fail to produce an effect.

    Fortunately, though, diffuse gliomas have one major weak point, as their cells tend to develop a specific mutation in more than 70 percent of patients. This mutation affects an enzyme called isocitrate dehydrogenase 1 (IDH1), causing it to change structure and morph into a novel protein called a neo-epitope. Crucially, this mutated IDH1 is only found in gliomas and does not occur in healthy tissue, which means the immune system recognizes it as foreign.

    The study authors therefore sought to develop a vaccine in order to trigger the formation of antibodies that can seek out and destroy this mutated protein.

    "Our idea was to support patients' immune system and to use a vaccine as a targeted way of alerting it to the tumor-specific neo-epitope," explained study author Michael Platten in a statement. Prior to conducting the trial, the team had already managed to synthesize the mutated IDH1 protein, using it to successfully vaccinate mice and halt the progression of IDH-1-mutated tumors.

    Writing in the journal Nature, the researchers explain how they administered their vaccine to 33 patients with IDH1-mutated glioma, as part of a Phase I trial. All participants received the vaccine alongside standard cancer treatments, and none experienced any side effects as a result of their participation in the study.

    Vaccine-induced immune responses were seen in 93.3 percent of patients, who developed large numbers of T cells with receptors that responded specifically to the mutated IDH1. In many participants, these immune cells invaded the brain tumors, causing them to swell.

    Most importantly, 84 percent of patients survived for three years following treatment, with 64 percent experiencing no growth in their tumors during this period. Of those who developed an immune response, 82 percent had a total cessation of tumor growth for two years after treatment.

    Platten insists that larger, placebo-controlled trials will be needed before any solid conclusions are drawn, although he and his colleagues are understandably highly encouraged by their findings. "The safety and immunogenicity of the vaccine were so convincing that we continued to pursue the vaccine concept in a further phase I study," he explained.

    This second study will see the IDH1 vaccine combined with checkpoint inhibitor immunotherapy, which generally boosts the immune system. According to Platten, this could potentiate the body’s immune response to the vaccine, thereby increasing the ability of white blood cells to destroy gliomas in the brain.

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