Immunotherapy Innovation Involving Checkpoint Inhibitors Gaining Momentum

A new innovation has shown great success in treating different kinds of tumors in mice that do not react to cancer immunotherapy medications, and they are called checkpoint inhibitors.

checkpoint inhibitors

Y-traps aim at the same proteins as existing checkpoint inhibitors: cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1)/PD-1 ligand (PD-L1). These proteins are known to assist Tregs, a certain type of white blood cell, in suppressing anti-tumor immune responses.

As a result, checkpoint inhibitors are expected to free the immune system to attack and kill tumor cells. Although in practice, they work only in some cancer patients.

A human immune system has the ability to find and eradicate cancer cells, unfortunately almost every form of cancer has adapted to this and can suppress the natural defense functions of the body.

The difference between Y-traps and checkpoint inhibitors is that Y-traps also join and neutralize transforming growth factor beta (TGFbeta) in addition to CTLA-4 or PD-1/PD-L1. TGFbeta is a protein that induces the activity of Tregs and inhibits anti-tumor immune cells. By trapping TGFbeta and restraining its activity, Y-traps improve the body’s own immune response to tumors even more than the existing checkpoint inhibitors. They are also designed to fight many different kinds of cancer.

One sort of Y-trap tested in mice is made of an antibody to CTLA-4 containing a TGFbeta “trap” in it. In the wake of transplanting human disease cells into mice, the specialists found that their Y-trap wiped out Tregs in tumors and hindered the development of tumors that had reacted unsuccessfully to Yervoy (ipilimumab), a checkpoint inhibitor that targets CTLA-4 as well.

Following that, they created a Y-trap that targets PD-L1 and traps TGFbeta. They found that their Y-trap works better than the checkpoint inhibitors Tecentriq or Bavencio that also target PD-L1. This particular Y-trap impeded the growth of tumors that had not responded to these medications.

This technology is just the start, scientists are continually advancing and inventing new ways of dealing with the problems that revolve around checkpoint inhibitors.