Functional Tuning of CARs Reveals Signaling Threshold above Which CD8+ CTL Antitumor Potency Is Attenuated due to Cell Fas-FasL-Dependent AICD

• Published in: Cancer immunology research Vol. 3; no. 4; p. 368
• Main Authors: Künkele, Annette, Johnson, Adam J, Rolczynski, Lisa S, Chang, Cindy A, Hoglund, Virginia, Kelly-Spratt, Karen S, Jensen, Michael C
• Format: Journal Article
• Language: English
• Published: United States 01.04.2015
• Subjects: Animals; Brain Neoplasms - immunology; Brain Neoplasms - therapy; Cell Line, Tumor; Cytotoxicity, Immunologic - immunology; Fas Ligand Protein - immunology; fas Receptor - immunology; Genetic Vectors; Humans; Lentivirus - genetics; Lymphocyte Activation - immunology; Mice, Inbred NOD; Mice, SCID; Neuroblastoma - immunology; Neuroblastoma - therapy; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Recombinant Fusion Proteins - immunology; Signal Transduction - immunology; T-Lymphocytes, Cytotoxic - immunology; Xenograft Model Antitumor Assays

Chimeric antigen receptor (CAR) development is biased toward selecting constructs that elicit the highest magnitude of T-cell functional outputs. Here, we show that components of CAR extracellular spacer and cytoplasmic signaling domain modulate, in a cooperative manner, the magnitude of CD8(+)CTL a...