Prostate Cancer Metastasis will be targeted by first-in-class Anti-sMIC immunotherapy

A research team has been investigating the mechanisms driving prostate cancer progression and have been developing novel treatments and models to combat metastasis for the past 15 years. The team has mechanistically examined how cancer cells have been able to bypass immune cells and survive. The work initially started with the discovery that in advanced stages of prostate cancer, the cancer cells could not only escape immune system surveillance, but could also disable the immune system response.

The research found that the underlying mechanisms for these events came from the oncogenic stress-induced molecule called “MIC.” When found in healthy cells, MIC is not expressed on cell surfaces. However, the researchers discovered that during cancer development, and even at very early stages, prostate cells start to express MIC. MIC’s primary function is to “flag down” the immune cells, particularly the natural killer and cytotoxic T cells, to initiate their response in fighting cancer cells. However, it was found that in stages of advanced prostate cancer, the cancer cells have “chopped off” or eliminated the ability of MIC to “flag down” the immune cells.

Therefore, the cancer cells are able to bypass immune surveillance and roam free. Then, detrimentally, cancer cells release a soluble form of MIC, called sMIC, which shuts down the immune system and this allows for the cancer cells to “dodge” immune cells. When considered together, the research team reasoned that these mechanisms may explain the non-responsiveness to immunotherapy in patients with advanced prostate cancer.

The team developed a first-in-class monoclonal antibody to target sMIC. In preclinical models, the antibody has been found to “revive” immune system function and eliminate prostate cancer metastasis to solve this problem. The antibody has already shown promise in controlling metastasis of cancer cells when administered solo, and even in non-responders to immunotherapy. When it has been administered in combination with an immune checkpoint blockade, a synergistic anti-tumor effect occurred where both agents work to restore immune function.

The team is also working toward bringing this anti-sMIC antibody from preclinical to clinical use in humans. Plans are to conduct a preclinical safety assessment for clinical trials, examine how the antibody would work with current standards of care for prostate cancer, and investigate how to use the antibody to tackle neuroendocrine prostate cancer, the most lethal type prostate cancer.

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