Related Experiment Video
Updated: Apr 21, 2026
Transduction and Expansion of Primary T Cells in Nine Days with Maintenance of Central Memory Phenotype
Published on: March 18, 2020
Safety of targeting ROR1 in primates with chimeric antigen receptor-modified T cells
Carolina Berger1, Daniel Sommermeyer2, Michael Hudecek3
1Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Medicine, University of Washington, Seattle, Washington. cberger@fhcrc.org.
Abstract:
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.
Insights
Chimeric antigen receptor T-cell (CAR-T) therapy shows promise for targeting ROR1(+) malignancies. Studies in nonhuman primates confirm ROR1 CAR-T cells are safe and effective for cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Adoptive T-cell therapy using chimeric antigen receptor T-cells (CAR-T) is a novel cancer immunotherapy approach.
- Identifying suitable cell surface targets that are tumor-specific and safe for CAR-T cell targeting remains a challenge.
- The orphan tyrosine kinase receptor ROR1 is expressed on various lymphatic and epithelial malignancies and plays a role in tumor cell survival.
Purpose of the Study:
- To evaluate the safety and efficacy of ROR1-specific CAR-T cells in a preclinical nonhuman primate model.
- To determine potential toxicities associated with targeting ROR1, considering its low-level expression in some adult tissues.
Main Methods:
- Genetic engineering of T cells to express a chimeric antigen receptor (CAR) targeting ROR1.
- Adoptive transfer of autologous ROR1 CAR-T cells into nonhuman primates.
- Monitoring for toxicity and assessing CAR-T cell accumulation in lymphoid tissues.
Main Results:
- ROR1 CAR-T cells did not induce overt toxicity in normal organs of nonhuman primates.
- CAR-T cells successfully accumulated in bone marrow and lymph nodes, sites where ROR1-positive B cells are present.
- ROR1 expression is conserved between humans and macaques, supporting the use of this model.
Conclusions:
- The study supports the clinical investigation of ROR1 CAR-T cell therapy for ROR1-positive cancers.
- Nonhuman primates are a valuable model for assessing the safety of engineered T-cell immunotherapies targeting conserved tumor-associated molecules.
