New approach boosts the fight against cancer in T cells

New mouse studies by researchers at the Monash Biomedicine Discovery Institute (BDI), Peter MacCallum Cancer Center, and Cold Spring Harbor Laboratory show that inhibition of the T cell protein tyrosine phosphatase 1B (PTP1B) is mobilized to help suppress tumor growth. Is shown.

Survey results are published in the journal Cancer detection “PTP1B is an intracellular checkpoint that limits anti-tumor immunity of T and CAR T cells... “

“Immunotherapy aimed at relieving inhibitory constraints on T cells has revolutionized cancer management,” the researchers write. “So far, these have focused on blocking cell surface checkpoints such as PD-1. Here we identify PTP1B as an intracellular checkpoint that is upregulated in tumor T cells. The increase indicates that it limits T cell proliferation and cytotoxicity and contributes to tumor growth. “

Their findings also show that inhibition of PTP1B can enhance the response to widely used cancer treatments that block PD-1 checkpoints on the surface of T cells.

Lead Author Dr. Tony Tiganis, professorBiochemistry and Molecular Biology, Monash, PD-1 blockade may be effective against many tumors, but not all patients respond and resistance may develop Said there is.

“More preclinical studies are needed, but our findings show that excellent results were achieved when PTP1B inhibition was combined with existing mouse immunotherapy,” Tiganis said. increase.

The authors have shown that inhibition of PTP1B also significantly improves the effectiveness of cell therapy using CAR T cells.

“An important next step in this task is to further define the effects of PTP1B deletion on CART and traditional T cells in humans. Dr. Florian Wiede, Principal Investigator and Lead Author of the Study at the Peter MacCallum Cancer Center. States:

“In summary, our study identifies PTP1B as an essential negative regulator of T cell function and an intracellular T cell checkpoint that limits antitumor immunity of tumor-infiltrating CD8 + T cells.” Those are saying. “Inhibition of PTP1B in cancer indicates that it can enhance endogenous T cell-mediated antitumor immunity, similar to that seen by targeting cell surface checkpoint PD-1, which revolutionized cancer treatment. In addition, inhibition of PTP1B or gene deletion can overcome the major hurdles that have previously limited the effectiveness of CAR T cells for solid tumors. “

Tiganis and Wiede are working with Cold Spring Harbor Laboratory and DepYmed, a US-based company that continues to develop PTP1B inhibitors, to check for new orally biologically available PTP1B inhibitor candidates. Test as a point inhibitor.

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