CAR mechanics: driving T cells into the MUC of cancer.
Several monoclonal antibodies bind in a highly selective manner to tumor-associated glycoforms of MUC1. We set out to exploit this by developing a MUC1-specific chimeric antigen receptor. Difficulties were encountered in this endeavor, owing to MUC1-imposed steric hindrance and antigenic heterogeneity. These issues were addressed by the iterative engineering of all components of the fusion receptor. Our experience underlines the need for careful individual optimization of immunotherapeutic reagents as dictated by the molecular vagaries of the target under study.
Maher
John
J
King's College London School of Medicine, Division of Cancer Studies, Research Oncology Section, Guy's Hospital Campus, London, United Kingdom. john.maher@kcl.ac.uk
Wilkie
Scott
S
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000235:genetics* / Q000276:immunology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008954:Models, Biological; D018396:Mucin-1 / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*
D018396:Mucin-1; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins