Li et al. identified broad expression of NKR ligands on ovarian tumor cells, motivating the application of allogeneic, IL-15+ CAR NKT cells, which were effective in CAR antigen+/- xenograft models, and exhibited strong tumor homing and retention. CAR NKT cells sustained an effector/memory phenotype in vivo, and induced minimal changes in tumor cells, while CAR T cells became exhausted and led to immune-evasive alterations and antigen loss. CAR NKT cells also uniquely modified the TME through deletion of CD1d+ TAMs/MDSCs. Unlike CAR T cells, CAR NKT cells led to minimal CRS and did not induce GvHD, while also evading allorejection.
Contributed by Morgan Janes
Author Info: (1) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los A
Author Info: (1) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (2) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (3) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (4) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (5) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (6) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (7) Department of Obstetrics and Gynecology, UCLA, Los Angeles, CA 90095, USA; Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA. (8) Department of Obstetrics and Gynecology, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA. (9) Department of Obstetrics and Gynecology, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA. (10) Bioinformatics Interdepartmental Program, UCLA, Los Angeles, CA 90095, USA. (11) Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA. (12) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (13) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (14) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (15) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (16) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (17) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA; Mork Family Department of Chemical Engineering and Materials Science, University of Southern California (USC), Los Angeles, CA 90089, USA. (18) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (19) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (20) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (21) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (22) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (23) Division of Cardiology, Department of Medicine, UCLA, Los Angeles, CA 90095, USA. (24) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (25) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (26) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (27) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA. (28) Department of Biomedical Engineering, University of California, Davis (UCD), Davis, CA 95616, USA; Department of Surgery, School of Medicine, UCD, Sacramento, CA 95817, USA; Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, CA 95817, USA. (29) Department of Obstetrics and Gynecology, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA. (30) Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA. (31) Section of Interventional Pulmonology, Keck School of Medicine, USC, Los Angeles, CA 90089, USA. (32) Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA. (33) Division of Cardiology, Department of Medicine, UCLA, Los Angeles, CA 90095, USA. (34) Department of Biomedical Engineering, University of California, Davis (UCD), Davis, CA 95616, USA; Department of Surgery, School of Medicine, UCD, Sacramento, CA 95817, USA; Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, CA 95817, USA. (35) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Division of Cardiology, Department of Medicine, UCLA, Los Angeles, CA 90095, USA; Human Genetics, UCLA, Los Angeles, CA 90095, USA. (36) Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA. (37) Department of Biostatistics, Fielding School of Public Health, UCLA, Los Angeles, CA 90095, USA. (38) Bioinformatics Interdepartmental Program, UCLA, Los Angeles, CA 90095, USA; Institute for Quantitative and Computational Biosciences-The Collaboratory, UCLA, Los Angeles, CA 90095, USA; Department of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA. (39) Mork Family Department of Chemical Engineering and Materials Science, University of Southern California (USC), Los Angeles, CA 90089, USA. (40) Department of Obstetrics and Gynecology, UCLA, Los Angeles, CA 90095, USA; Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA; The VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA; Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA 90095, USA. Electronic address: smemarzadeh@mednet.ucla.edu. (41) Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Bioengineering, UCLA, Los Angeles, CA 90095, USA; Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA; Parker Institute for Cancer Immunotherapy, UCLA, Los Angeles, CA 90095, USA; Goodman-Luskin Microbiome Center, UCLA, Los Angeles, CA 90095, USA. Electronic address: liliyang@ucla.edu.
