might interest some, figured this could be the place (link from @MichaelSMagee).....
Cancer Immunol Res. 2014 Oct 29. pii: canimm.0163.2014. [Epub ahead of print]
Safety of targeting ROR1 in primates with chimeric antigen receptor-modified T cells.
Berger C1, Sommermeyer D2, Hudecek M3, Berger M4, Balakrishnan A4, Paszkiewicz PJ5, Kosasih PL2, Rader C6, Riddell SR7.
1Clinical Research Division - Program in Immunology, Fred Hutchinson Cancer Research Center cberger@fhcrc.org.
2Clinical Research Division, Program in Immunology, Fred Hutchinson Cancer Research Center.
3Department of Medicine II - Hematology and Medical Oncology, University of Würzburg.
4Clinical Research Division - Program in Immunology, Fred Hutchinson Cancer Research Center.
5Institute for Medical Microbiology, Immunology, and Hygiene, Technical University of Munich.
6Florida Campus, Department of Cancer Biology, The Scripps Research Institute.
7Program in Immunology, Fred Hutchinson Cancer Research Center.
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) since 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. |
