Radiotherapy of human xenograft NSCLC tumors in nude mice with a 90Y-labeled anti-tissue factor antibody.
Tissue factor (TF) is a type I transmembrane protein and the initiator of the extrinsic blood coagulation pathway. TF plays a critical role in tumor development and its overexpression is observed in many tumors. To understand the prevalence and relative level of TF expression in non-small-cell lung cancer (NSCLC), we analyzed 50 NSCLC tumors by immunohistochemical staining and found that 88% of human NSCLC tumors overexpressed TF. We then generated a high affinity anti-TF antibody, TF278, which specifically binds TF on the surface of cells and is internalized upon binding. An 111In-labeled TF278 demonstrated favorable tumor accumulation in an SW-900 xenograft tumor model with a maximum mean percent of injected dose per gram of tissue (%ID/g) of 73.1% at 96 hours postinjection. In addition, we labeled the antibody with 90Y and tested its ability to inhibit the growth of tumors in an SW-900 xenograft tumor model in immunocompromised mice. The 90Y-TF278 slowed the growth of SW-900 tumors at a 50 microCi dose and completely regressed SW-900 tumors at a 150 microCi dose with little toxicity.
BioRexis Pharmaceutical Corporation, King of Prussia, PA 19406, USA. bwang@biorexis.com
Baiyang
B
Wang
Marc
M
Berger
Gregg
G
Masters
Earl
E
Albone
Qifeng
Q
Yang
Josephine
J
Sheedy
Yolanda
Y
Kirksey
Lisa
L
Grimm
Bo
B
Wang
Judith
J
Singleton
Daniel
D
Soltis
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy*; D004705:Endocytosis; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011829:Radiation Dosage; D013925:Thromboplastin / Q000276:immunology*; D014018:Tissue Distribution; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays; D015021:Yttrium Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use
D000906:Antibodies; D000941:Antigens; D015021:Yttrium Radioisotopes; D013925:Thromboplastin