American Association for Cancer Research
23266066cir140163-sup-135488_1_supp_2682243_ncq67y.pdf (119.34 kB)

Supplementary Figure Legends from Safety of Targeting ROR1 in Primates with Chimeric Antigen Receptor–Modified T Cells

Download (119.34 kB)
journal contribution
posted on 2023-04-03, 23:04 authored by Carolina Berger, Daniel Sommermeyer, Michael Hudecek, Michael Berger, Ashwini Balakrishnan, Paulina J. Paszkiewicz, Paula L. Kosasih, Christoph Rader, Stanley R. Riddell

Supplementary Figure Legends



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.

Usage metrics

    Cancer Immunology Research



    Ref. manager