Premium
Enhancing the anti‐tumor efficacy of chimeric antigen receptor‐expressing T cells with naturally occurring plant stilbenes
Author(s) -
Soles Andrea,
Richardson Elle,
Barber Amorette
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.792.14
Subject(s) - chimeric antigen receptor , proinflammatory cytokine , cancer research , cancer cell , immune system , biology , receptor , antigen , t cell , cancer , immunology , chemistry , inflammation , biochemistry , genetics
Despite advances in treatment options, cancer remains the second leading cause of death in the United States. Many therapies use immune cells, specifically T cells, for cancer therapy. To enhance tumor recognition by T cells, chimeric antigen receptors consisting of signaling domains fused to receptors that recognize tumor antigens can be created and expressed in T cells. One receptor that is a prospective target for a chimeric antigen receptor is PD1 because the ligands for the PD1 receptor are expressed on many cancer types. Our lab has genetically engineered a chimeric PD1 (chPD1) receptor and has shown that chPD1‐expressing T cells kill tumor cells, secrete inflammatory cytokines, reduce tumor burden, and increase survival in multiple tumor types. A current focus of cancer research is the development of combination therapies that enhance anti‐tumor efficacy without increasing harmful side effects. Recently, a family of naturally occurring plant compounds called stilbenes have been shown to enhance T cell function. Therefore, we tested if stilbenes enhanced chPD1 T cell function in breast cancer. Addition of resveratrol, a stilbene found in berries, grapes, peanuts, and other plants, decreased proliferation, enhanced tumor cell killing, and increased secretion of proinflammatory cytokines (IFNγ, GM‐CSF, TNFα, IL‐17, IL‐2, and IL‐21) from chPD1 T cells. Presence of resveratrol also increased skewing of T cell differentiation to a central memory phenotype through reduction of AKT and mTORc1 signaling, reduced expression of T‐bet and BLIMP‐1 transcription factors, and increased expression of Bcl‐6 and Eomes transcription factors. Hence, combination of resveratrol and chimeric antigen receptor‐expressing T cells may enhance anti‐tumor immune responses through inhibition of the AKT and mTORc1 pathways and skewing to a long‐lived central memory phenotype. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .