Center for Synthetic Immunity - Projects

Although CAR T cell therapy can be very effective, there have been clinical reports of significant toxicity. Defining molecular mechanisms associated with toxicity following CAR infusion may lead to novel treatments or formulations to improve the safety of CAR therapy.

We have discovered key mechanisms that may control the extent of cytokine storm in CAR T cell treated animals. We are exploring additional mechanisms using CARs that target different antigens to understand the nature of CAR T cell toxicity and test new ways to prevent these adverse events following CAR T cell infusion.

Allogeneic T cell CAR platforms:

Not every patient has robust T cells that permit the use of autologous cells for CAR therapy.  The development of technologies that enable the use of healthy allogeneic T cells as a source of CAR effector cells while avoiding potential Graft-versus-Host-Disease (GVHD) would improve the manufacturing and affordability of CAR cell therapy.

We are developing TIM (T cell inhibitory molecules) technology to allow the use of CAR T cells without GVHD yet retain excellent therapeutic efficacy.

A basic CAR platform consists of:

  • a recognition protein
  • a regulatory protein
  • a marker or safety gene

All types of cancer can be targeted by chimeric antigen receptor (CAR) effector cells. CARs are receptors designed to recognize specific target molecules on tumor cells and activate immune cells. CARs direct killing of tumor cells and local cytokine production that results in tumor eradication and fundamentally alters the tumor microenvironment to induce host anti-tumor immunity and inhibit tumor cell growth.