Targeted cancer therapies can suppress T cell immune responses, study finds
pharmafile | March 23, 2016 | News story | Research and Development | T cell, anti-cancer drugs, immunosuppresive, superagonist, wistar institute
Researchers at the Wistar Institute have developed a new method whereby targeted cancer therapies can provide appropriate therapeutics without supressing the T cells that can help to fight tumours.
While targeted therapies are often preferred over chemotherapy and surgery because they attack and kill cancer cells while sparing healthy, normal cells that do not express these mutations, the research team highlighted that dozens of these targeted therapies suppressed the activity of T cells. These cells could actually help fight tumours.
Program leader professor Jose R. Conejo-Garcia comments: “We wanted to know what the consequences to the immune system were when tumour cells were exposed to targeted therapies. The effect that these drugs have on the interplay between tumour cells and leukocytes, which are essential for controlling the growth of immunogenic tumours, must be understood if we are to maximise the benefits of combination or sequential administration of targeted therapies and immunotherapies.”
While studying the FDA-approved targeted therapy trametinib (marketed as Mekinist by GSK, and later Novartis), the team found that pairing it with a signalling protein “superagonist” stimulated T cell activity while preserving the cancer-blocking effects of the cancer treatment.
The researchers studied 41 different small molecule inhibitors and their effects on healthy human T cells and found that all of them inhibited T cells more potently than cancer cells. Mekinist, which is a MEK1/2 inhibitor approved to treat metastatic melanoma with a specific mutation that affects half of all patients with melanoma, was a particularly powerful inhibitor of T cell activity.
Mihael Allegrezza, first author of the study, adds: “MEK inhibitors like trametinib are being tested in a variety of tumours, and we’ve demonstrated an effective means of controlling the effect that these drugs have on T cells that could further help in the fight against cancer.”
The study results were published in the journal Cancer Research.
Sean Murray
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