title: Redirecting gene-modified T cells toward various cancer types using tagged antibodies.
abstract: OBJECTIVE
  To develop an adaptable gene-based vector that will confer immune cell specificity to various cancer types.
  
  
  METHODS
  Human and mouse T cells were genetically engineered to express a chimeric antigen receptor (CAR) that binds a fluorescein isothiocyanate (FITC) molecule, termed anti-FITC CAR T cells. Various antibodies (Ab) currently in clinical use including cetuximab (Ctx), trastuzumab (Her2), and rituximab (Rtx) were conjugated with FITC and tested for their ability to bind tumor cells, activate T cells, and induce antitumor effects in vitro and in vivo.
  
  
  RESULTS
  Anti-FITC CAR T cells recognize various cancer types when bound with FITC-labeled Abs resulting in efficient target lysis, T-cell proliferation, and cytokine/chemokine production. The treatment of immunocompromised mice with human anti-FITC CAR T cells plus FITC-labeled cetuximab (FITC-Ctx) delayed the growth of colon cancer but unexpectedly led to the outgrowth of EGF receptor (EGFR)-negative tumor cells. On the other hand, in a human pancreatic cancer cell line with uniform EGFR expression, anti-FITC CAR T cells plus FITC-Ctx eradicated preestablished late-stage tumors. In immunocompetent mice, anti-FITC CAR T cells exhibited potent antitumor activity against syngeneic mouse breast cancer expressing Her2 and B-cell lymphoma expressing CD20 by combining with FITC-Her2 and FITC-Rtx, respectively. In addition, the activity of anti-FITC CAR T cells could be attenuated by subsequent injections of nonspecific FITC-IgG.
  
  
  CONCLUSIONS
  These studies highlight an applicability of anti-tag CAR technology to treat patients with different types of cancers and a possibility to regulate CAR T-cell functions with competing FITC molecules.
authors.affiliation: Marlene and Stewart Greenebaum Cancer Center, Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland, Baltimore, Maryland 21201, USA.
authors.forename: Koji
authors.initials: K
authors.lastname: Tamada
authors.forename: Degui
authors.initials: D
authors.lastname: Geng
authors.forename: Yukimi
authors.initials: Y
authors.lastname: Sakoda
authors.forename: Navneeta
authors.initials: N
authors.lastname: Bansal
authors.forename: Ratika
authors.initials: R
authors.lastname: Srivastava
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Li
authors.forename: Eduardo
authors.initials: E
authors.lastname: Davila
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D011946:Receptors, Antigen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D016207:Cytokines; D011946:Receptors, Antigen