Data from AXL inhibition improves the anti-tumor activity of chimeric antigen receptor T cells

• DOI: 10.1158/2326-6066.c.6765339.v3
• Publication Date: 2024-09-16T09:53:47Z
• Authors: R. Leo Sakemura; Mehrdad Hefazi; Michelle J. Cox; Elizabeth L. Siegler; Sutapa Sinha; Michael J. Hansen; Carli M. Stewart; Jennifer M. Feigin; Claudia Manriquez...; Kendall J. Schick; Ismail Can; Erin E. Tapper; Paulina Horvei; Mohamad M. Adada; Evandro D. Bezerra; Lionel Aurelien. ...; Michael W. Ruff; Cynthia L. Forsman; Wendy K. Nevala; Justin C. Boysen; Renee C. Tschumper; Cory L. Grand; Kamesh R. Kuchima...; Lars Mouritsen; Jason M. Foulks; Steven L. Warner; Timothy G. Call; Sameer A. Parikh; Wei Ding; Neil E. Kay; Saad S. Kenderian

<div>Abstract<p>The receptor tyrosine kinase AXL is a member of the TAM (Tyro3, AXL, and proto-oncogene tyrosine-protein Mer) family plays pleiotropic roles in cancer progression. expressed immunosuppressive cells, which contributes to decreased efficacy immunotherapy. Therefore, we hypothesized that inhibition could serve as strategy overcome resistance chimeric antigen T (CART)-cell therapy. To test this, determined impact on CD19-targeted CART (CART19)-cell functions. Our results demonstrate cells express high levels AXL. Specifically, higher activated Th2 M2-polarized macrophages were observed. with small molecules or via genetic disruption demonstrated selective cytokines, reversal CART-cell inhibition, promotion effector novel enhance functions through two independent, but complementary, mechanisms: targeting reversing myeloid-induced macrophages.</p></div>