A new immunological checkpoint has been found by the Monash Biomedicine Discovery Institute (BDI) researchers, which could be used to treat cancer.

The findings reveal that by suppressing the protein tyrosine phosphatase PTP1B in T cells, the body’s immunological response to cancer can be activated, assisting in tumor growth suppression.

T cells are an important part of the body’s immune system. They help kill invaders like viruses, but they also help fight cancer cells, too. This study, on the other hand, found that when a new drug candidate is used, the amount of PTP1B in T cells that enter tumors rises, which limits the ability of T cells to fight cancer. These findings show that PTP1B is an intracellular brake, or checkpoint, like the cell surface checkpoint PD-1, which has changed the way we treat cancer.

Scientists from Monash BDI, in collaboration with colleagues from the Peter MacCallum Cancer Centre in Melbourne and Cold Spring Harbor Laboratory in New York, discovered that inhibiting PTP1B, using an early-stage injectable drug candidate that has previously been shown to be safe and well-tolerated in humans, improves T cells’ cancer-fighting ability, suppressing tumor growth.

Surprisingly, the authors discovered that inhibiting PTP1B, an internal checkpoint, can improve the response to a commonly used cancer medication that inhibits the PD-1 checkpoint on T cells’ surfaces.

A study’s senior author says that even though blocking PD-1 can be very effective against many types of tumors, not all patients respond and resistance is common. This is true even for tumors that are responsive to immunotherapy, such as melanoma. In the clinic, approaches that can increase the effectiveness or duration of action of PD-1 checkpoint blockage are greatly desired.

“While more pre-clinical work is needed, our findings show that superior outcomes were achieved when we combined PTP1B inhibition with existing immunotherapies in mice,” says Professor Tiganis.

Furthermore, the authors found that inhibiting PTP1B improved the efficiency of cellular therapy using Chimeric Antigen Receptor (CAR) T cells, in addition to improving the response to PD-1 blocking.

These T cells come from a person’s blood and are changed in the lab to make them produce a man-made receptor that helps them better find tumor cells. They are then injected back into the person. 

Although CAR T cells have shown to be highly effective against some blood cancers, this success has yet to be replicated in solid tumors. The researchers show that knocking out or inhibiting PTP1B improves the ability of CAR T cells to fight solid tumors in mice.

“To advance this work, a key next step will be to further define the impact of PTP1B deletion in CAR T and conventional T cells in humans. There remains an urgent clinical need to identify and validate cellular targets to revive and sustain T cell responses in cancer,” adds first author Dr. Florian Wiede.

Source: 10.1158/2159-8290.CD-21-0694

Image Credit: Getty

You were reading: New immune checkpoint could be exploited for cancer therapy