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Triple Combination immunotherapy improves results of the treatment of melanoma

November 30, 2018 14:28

Adoptive transfer of cells - is a promising cancer immunotherapy, which includes selection of more active T cells, increasing their number in the lab, and then back to the transporting patients. The technique is already available for some diseases - a CAR T-therapy approved for children with acute lymphoblastic leukemia and adults with the development of lymphoma.

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Combination therapy with an inhibitor of the Pan-PIM-Kinase inhibitor and PD1 improves results in preclinical models, according to researchers at the Medical University of South Carolina in an article published in Clinical Cancer Research. They showed that the three-component combination therapy doubled the T cell migration to the tumor and increase survival in mice four times.

"When the triple combination therapy was maintained for many more T cells," - says Shikhar Mehrotra, senior author of the paper and director of the cancer immunotherapy programs at the Department of Surgery, Medical University of South Carolina.

Clinical progress with checkpoint inhibitors, including inhibitors of PD1 and PDL1, immunotherapy opened as the fifth stage of cancer therapy (other stages - chemotherapy, surgery, radiotherapy and targeted therapy). Due inhibitors PD1 and PDL1 T cells "see" a tumor.

Conversely, inhibitors of PIM kinases are a relatively new therapy. PIM kinases - are proteins that can control many cellular processes, including energy. Clinical control unit for the new therapy has been the lack of energy in the T-cells.

"T-cell that begins to multiply, like a man who starts his day with a lot of energy - explains Mehrotra. - As a person, the T cell can be "tired" and less effective. We wondered whether the PIM kinase inhibitors can prevent it. "

Mehrotra and other researchers targeting PIM kinases in T cells to cause them to act as subtype specific T cells, called the central memory T cell. Most tests use a rapidly expanding T-cells (T-cells, which are ready to attack the tumor), but these T cells are often exhausted when they return to the patients. central memory T cells produce longer responses against tumor cells. When scientists blocked the PIM kinases in T cells, the cells began to act as a memory T-cells, as evidenced by the increase in populations of cells.

"All cells need energy - said Mehrotra. - You can control the way of using the T cell with its energy. In this case, we are focused on PIM kinases and have shown that in combination with the control treatment we get a better response and control of the tumor. "

Indeed, in a mouse model of triple combination therapy to better control the growth of melanoma than PIM kinase inhibitors alone.

"Ultimately, we want to implement this therapeutic approach in the clinic - said Mehrotra. - However, first we need to investigate any potential side effects of pan-PIM-Kinase inhibitors. "



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