The Relationship Between CAR-Modified CD4 and CD8 T Cells in B-Cell Malignancies

Cameron J. Turtle, MD, PhD, assistant member, Fred Hutchinson Cancer Research Center, assistant professor, University of Washington, discuses the relationship between CD4 and CD8 T cells in patients with B-cell malignancies.

Turtle says that CD4 and CD8 are two subsets of T cells that work in slightly different ways. Mouse trials have shown that CD4 and CD8 work together more effectively than on their own, particularly when used together in a chimeric antigen receptor (CAR) setting.

In the 2639 study, CD4 and CD8 T cells are taken from patients with B-cell malignancies and engineered into CAR-modified T cells before they are given back to the patient, Turtle says. In order to study the cooperation between the CD4 and CD8 T cells, each is engineered separately before they are mixed together to try to get an optimal effect on the tumor.

In the 2494 study, patients with b-cell malignancies are treated with CAR-modified T cells taken from a donor’s blood instead. Turtle says the 2949 study is done in the same fashion as the 2639 study, except that researchers have to be careful about the risk of graft-versus-host disease (GVHD). Even when modified, these T cells still possess their native receptors and the risk of alloreactivity is still present, Turtle suggests.

In order to combat this, researchers are stimulating T cells with a peptide for common viruses such as Cytomegalovirus (CMV) and Epstein-Barr (EBV) in addition to CAR to narrow down the T cell receptor range that can potentially cause GVHD.

Clinical Pearls

• CD4 and CD8 are two subsets of T cells that work in slightly different ways
• Mouse trials have shown that CD4 and CD8 T cells work better together in CAR-engineered cells
• Treatment approaches with autologous and allogeneic CAR-modified T cells are under investigation
• To reduce alloreactivity and the risk of GVHD, the CAR-modified T cells are further altered with CMV and EBV