Anti-tax interacting protein-1 (TIP-1) monoclonal antibody targets human cancers.
Radiation-inducible neo-antigens are proteins expressed on cancer cell surface after exposure to ionizing radiation (IR). These neo-antigens provide opportunities to specifically target cancers while sparing normal tissues. Tax interacting protein-1 (TIP-1) is induced by irradiation and is translocated to the surface of cancer cells. We have developed a monoclonal antibody, 2C6F3, against TIP-1.Epitope mapping revealed that 2C6F3 binds to the QPVTAVVQRV epitope of the TIP-1 protein. 2C6F3 binds to the surface of lung cancer (A549, LLC) and glioma (D54, GL261) cell lines. 2C6F3 binds specifically to TIP-1 and ELISA analysis showed that unconjugated 2C6F3 efficiently blocked binding of radiolabeled 2C6F3 to purified TIP-1 protein. To study in vivo tumor binding, we injected near infrared (NIR) fluorochrome-conjugated 2C6F3 via tail vein in mice bearing subcutaneous LLC and GL261 heterotopic tumors. The NIR images indicated that 2C6F3 bound specifically to irradiated LLC and GL261 tumors, with little or no binding in un-irradiated tumors.We also determined the specificity of 2C6F3 to bind tumors in vivo using SPECT/CT imaging. 2C6F3 was conjugated with diethylene triamine penta acetic acid (DTPA) chelator and radiolabeled with 111Indium (111In). SPECT/CT imaging revealed that 111In-2C6F3 bound more to the irradiated LLC tumors compared to un-irradiated tumors. Furthermore, injection of DTPA-2C6F3 labeled with the therapeutic radioisotope, 90Y, (90Y-DTPA-2C6F3) significantly delayed LLC tumor growth. 2C6F3 mediated antibody dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cell-mediated phagocytosis (ADCP) in vitro.In conclusion, the monoclonal antibody 2C6F3 binds specifically to TIP-1 on cancer and radio-immunoconjugated 2C6F3 improves tumor control.
Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri, USA.
Heping
H
Yan
Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri, USA.
Vaishali
V
Kapoor
Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri, USA.
Kim
K
Nguyen
Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri, USA.|Siteman Cancer Center, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, USA.
Walter J
WJ
Akers
Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri, USA.
Hua
H
Li
Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri, USA.
Jalen
J
Scott
Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri, USA.
Richard
R
Laforest
Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri, USA.
Buck
B
Rogers
Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri, USA.|Siteman Cancer Center, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, USA.
Dinesh
D
Thotala
Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri, USA.|Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri, USA.|Siteman Cancer Center, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, USA.
Dennis
D
Hallahan
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology / Q000528:radiation effects; D000074322:Antineoplastic Agents, Immunological / Q000493:pharmacokinetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000379:methods*; D000072098:Single Photon Emission Computed Tomography Computed Tomography; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000074322:Antineoplastic Agents, Immunological; D007205:Indium Radioisotopes; D047908:Intracellular Signaling Peptides and Proteins; C421249:TAX1BP3 protein, human
TIP-1; in vivo imaging; monoclonal antibody; radiation-inducible; radioimmunotherapy