Dr. Kim on the Synergistic Effect of PD-1H Blockade in AML

Tae Kon Kim, MD, PhD, assistant professor of medicine, Division of Hematology and Oncology, assistant professor of pathology, microbiology and immunology, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, discusses key results on the synergistic effects of PD-1H blockade in acute myeloid leukemia (AML).

Previous research has shown that the PD-1H surface protein is expressed on AML blasts, inhibiting T-cell immunity and leading to immune evasion, Kim begins.

To build on these findings, a series of knockout (KO) experiments were performed in mouse models, Kim says. The study aimed to confirm the expression of PD-1H on normal myeloid cells and T cells in bone marrow and evaluate the role of the host immune cell PD-1H in immune evasion of AML.

Genetically modified mice with either wild-type or PD-1H knockout immune cells underwent transplantation with AML cells, Kim says. Lineage-specific conditional KO mice were then generated. This population did not express PD-1H in either T cells or myeloid cells. In vivo proliferation was then assessed in both conditional KO and control mice using bioluminescence. AML proliferation was found to be significantly decreased in PD-1H mice with myeloid cell-specific KO compared with wild-type mice, Kim states. This indicates that immune evasion is associated with PD-1H expression on host myeloid cells rather than T cells, he explains.

The potential synergistic effects of PD-1H blockade were then explored in KO mice treated with aPD-1H and PD-1 blockade alone vs in combination, Kim continues. PD-1H blockade alone was found to significantly suppress in vivo growth of AML compared with the control group, while the combination was found to have a synergistic effect on in vivo growth vs anti–PD-1 alone, he says.

Lastly, a humanized AML model was designed to assess the effect of human PD-1H blockade, Kim details. The human PD-1H antibody was also found to produce synergistic effects combined with human PD-1 antibodies, Kim states.

Overall, these findings indicate that anti–PD-1H exhibits greater anti-leukemia activity compared with anti–PD-1 alone. Future research should continue exploring the anti-tumor activity and efficacy of PD-1 and PD-1H combination therapies in this tumor type, Kim concludes.

Editor’s Note: Dr. Kim reports serving as a consultant for Agenus and receiving funding from Nextcure.