TY - JOUR T1 - Safety of Targeting ROR1 in Primates with Chimeric Antigen Receptor–Modified T Cells JF - Cancer Immunology Research JO - Cancer Immunol Res SP - 206 LP - 216 DO - 10.1158/2326-6066.CIR-14-0163 VL - 3 IS - 2 AU - Berger, Carolina AU - Sommermeyer, Daniel AU - Hudecek, Michael AU - Berger, Michael AU - Balakrishnan, Ashwini AU - Paszkiewicz, Paulina J. AU - Kosasih, Paula L. AU - Rader, Christoph AU - Riddell, Stanley R. Y1 - 2015/02/01 UR - http://cancerimmunolres.aacrjournals.org/content/3/2/206.abstract N2 - Genetic engineering of T cells for adoptive transfer by introducing a tumor-targeting chimeric antigen receptor (CAR) is a new approach to cancer immunotherapy. A challenge for the field is to define cell surface molecules that are both preferentially expressed on tumor cells and can be safely targeted with T cells. The orphan tyrosine kinase receptor ROR1 is a candidate target for T-cell therapy with CAR-modified T cells (CAR-T cells) because it is expressed on the surface of many lymphatic and epithelial malignancies and has a putative role in tumor cell survival. The cell surface isoform of ROR1 is expressed in embryogenesis but absent in adult tissues except for B-cell precursors and low levels of transcripts in adipocytes, pancreas, and lung. ROR1 is highly conserved between humans and macaques and has a similar pattern of tissue expression. To determine if low-level ROR1 expression on normal cells would result in toxicity or adversely affect CAR-T cell survival and/or function, we adoptively transferred autologous ROR1 CAR-T cells into nonhuman primates. ROR1 CAR-T cells did not cause overt toxicity to normal organs and accumulated in bone marrow and lymph node sites, where ROR1-positive B cells were present. The findings support the clinical evaluation of ROR1 CAR-T cells for ROR1+ malignancies and demonstrate the utility of nonhuman primates for evaluating the safety of immunotherapy with engineered T cells specific for tumor-associated molecules that are homologous between humans and nonhuman primates. Cancer Immunol Res; 3(2); 206–16. ©2014 AACR. ER -