Chimeric PD1 Expressing T Cells for as a Therapy for Diffuse Large B Cell Lymphoma, Acute Myeloid Leukemia, and Acute Lymphocytic Leukemia

Haley Bresnahan, Arleigh Wood, Dr. Amorette Barber, Department of Biological and Environmental Sciences, Longwood University, 201 High Street, Farmville, VA, 23909

CD8 T cells are one of the immune system’s best defense mechanisms against tumors. However, some tumors evade T-cell detection by downregulating proteins that T cells use to identify tumors. Despite this, a majority of tumors express proteins called Programmed Death 1 (PD1) Ligands. Since PD1 ligands are expressed on most tumor types, and not on many other cells, they are ideal targets for potential therapies. One such therapy is the development of chimeric antigen receptors (CAR). CARs are modified receptors that use genetic engineering to replace the signaling domain in a protein. We developed a CAR with the PD1 receptor as the tumor-targeting domain attached to CD3 zeta activation and Dap10 costimulatory domains, called chimeric-PD1 receptor (chPD1). Previously, chPD1 expressing T cells were shown to effectively treat murine models of solid tumors including melanoma and pancreatic, kidney, colon, and prostate cancer. The purpose of the study was to test the anti-tumor efficacy of chPD1 T cells against murine Diffuse Large B cell Lymphoma (DLBCL), Acute Myeloid Leukemia (AML), and Acute Lymphocytic Leukemia (ALL). Flow cytometry and RTPCR were used to determine that DLBCL, AML, and ALL cell lines expressed PD1 ligands. Therefore, these tumor cells were potential targets for our chPD1 T cells. Using LDH cytotoxicity assays, we demonstrated that chPD1 T cells increased lysis of the tumor cells compared to wild type T cells. ELISAs and a LEGENDplex assay were used to assess the levels of cytokine secretion by chPD1 T cells and wild type T cells. For all tumor types tested, chPD1 T cells also secreted more pro-inflammatory cytokines, including IFN-γ, TNF-α, and GM-CSF, but did not secrete the anti-inflammatory cytokine IL-10. Therefore, chPD1 T cells could be a novel therapeutic strategy to treat Diffuse Large B cell Lymphoma, Acute Myeloid Leukemia, and Acute Lymphocytic Leukemia.

Additional Abstract Information

Presenters: Haley Bresnahan, Arleigh Wood

Institution: Longwood University

Type: Poster

Subject: Biology

Status: Approved

Time and Location

Session: Poster 3
Date/Time: Mon 4:30pm-5:30pm
Session Number: 3149