Publications
Cancer cellDec 2023 DOI:
10.1016/j.ccell.2023.11.011

Immune determinants of CAR-T cell expansion in solid tumor patients receiving GD2 CAR-T cell therapy

Kaczanowska, Sabina; Murty, Tara; Alimadadi, Ahmad; Contreras, Cristina F; Duault, Caroline; Subrahmanyam, Priyanka B; Reynolds, Warren; Gutierrez, Norma A; Baskar, Reema; Wu, Catherine J; Michor, Franziska; Altreuter, Jennifer; Liu, Yang; Jhaveri, Aashna; Duong, Vandon; Anbunathan, Hima; Ong, Claire; Zhang, Hua; Moravec, Radim; Yu, Joyce; Biswas, Roshni; Van Nostrand, Stephen; Lindsay, James; Pichavant, Mina; Sotillo, Elena; Bernstein, Donna; Carbonell, Amanda; Derdak, Joanne; Klicka-Skeels, Jacquelyn; Segal, Julia E; Dombi, Eva; Harmon, Stephanie A; Turkbey, Baris; Sahaf, Bita; Bendall, Sean; Maecker, Holden; Highfill, Steven L; Stroncek, David; Glod, John; Merchant, Melinda; Hedrick, Catherine C; Mackall, Crystal L; Ramakrishna, Sneha; Kaplan, Rosandra N
Product Used
Genes
Abstract
Chimeric antigen receptor T cells (CAR-Ts) have remarkable efficacy in liquid tumors, but limited responses in solid tumors. We conducted a Phase I trial (NCT02107963) of GD2 CAR-Ts (GD2-CAR.OX40.28.z.iC9), demonstrating feasibility and safety of administration in children and young adults with osteosarcoma and neuroblastoma. Since CAR-T efficacy requires adequate CAR-T expansion, patients were grouped into good or poor expanders across dose levels. Patient samples were evaluated by multi-dimensional proteomic, transcriptomic, and epigenetic analyses. T cell assessments identified naive T cells in pre-treatment apheresis associated with good expansion, and exhausted T cells in CAR-T products with poor expansion. Myeloid cell assessment identified CXCR3+ monocytes in pre-treatment apheresis associated with good expansion. Longitudinal analysis of post-treatment samples identified increased CXCR3- classical monocytes in all groups as CAR-T numbers waned. Together, our data uncover mediators of CAR-T biology and correlates of expansion that could be utilized to advance immunotherapies for solid tumor patients.
Product Used
Genes

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