Basic StudiesEnhanced Tumor Trafficking of GD2 Chimeric Antigen Receptor T Cells by Expression of the Chemokine Receptor CCR2bCraddock, John A.; Lu, An; Bear, Adham; Pule, Martin; Brenner, Malcolm K.; Rooney, Cliona M.; Foster, Aaron E. Author Information Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, TX This research was funded by Hope Street Kids Foundation Research Award (A.E.F.), T32 HL092332 and K12 CA090433 (J.A.C.), and the NIH/NCI 2 P01 CA094237-06 (M.K.B. and A.E.F.). Reprints: Aaron E. Foster, Center for Cell and Gene Therapy, Baylor College of Medicine, 1102 Bates Street, Houston, TX 77030 (e-mail: [email protected]). Received for publication April 14, 2010; accepted June 21, 2010 All authors have declared that there are no financial conflicts of interest in regards to this study. The authors declare no conflict of interest. Journal of Immunotherapy: October 2010 - Volume 33 - Issue 8 - p 780-788 doi: 10.1097/CJI.0b013e3181ee6675 Buy Metrics Abstract For adoptive T-cell therapy to be effective against solid tumors, tumor-specific T cells must be able to migrate to the tumor site. One requirement for efficient migration is that the effector cells express chemokine receptors that match the chemokines produced either by tumor or tumor-associated cells. In this study, we investigated whether the tumor trafficking of activated T cells (ATCs) bearing a chimeric antigen receptor specific for the tumor antigen GD2 (GD2-CAR) could be enhanced by forced coexpression of the chemokine receptor CCR2b, as this receptor directs migration toward CCL2, a chemokine produced by many tumors, including neuroblastoma. Neuroblastoma cell lines (SK-N-SH and SK-N-AS) and primary tumor cells isolated from 6 patients all secreted high levels of CCL2, but GD2-CAR transduced ATCs lacked expression of CCR2 (<5%) and migrated poorly to recombinant CCL2 or tumor supernatants. After retroviral transduction, however, ATCs expressed high levels of CCR2b (>60%) and migrated well in vitro. We expressed firefly luciferase in CCR2b-expressing ATCs and observed improved homing (>10-fold) to CCL2-secreting neuroblastoma compared with CCR2-negative ATCs. As a result, ATCs co-modified with both CCR2b and GD2-CAR had greater antitumor activity in vivo. © 2010 Lippincott Williams & Wilkins, Inc.