Albert Einstein Cancer Center

Radioimmunotherapy with antibody to HPV16 E6 oncoprotein is effective in experimental cervical tumor expressing low levels of E6

HP V16 is associated with about half of all cervical cancers worldwide. The E6 and E7 genes of oncogenic HP V types, such as HP V16, are necessary for the HP V transforming function and tumorigenesis making them ideal targets. AECC investigators Dadachova, Casadevall, Goldberg, Einstein and colleagues have used  radiolabeled monoclonal antibodies (mAbs) that bind to tumor-associated intracellular antigens as radiopharmaceuticals. In an earlier study they effectively targeted these viral antigens with a mAb to HP V16 E6 to suppress CasKi cervical tumors expressing ~600 copies of HP V per cell. However, the question remained as to whether radioimmunotherapy would be effective with low expression of E6 and E7, more relevant to the clinic. In this study, these investigators established that expression of E6 in tumors from patients and in the SiHa cell line expressed comparable low levels of E6 and E7 (1-2 copies of HP V per cell). They then tested the efficacy of a radiopharmaceutical against SiHa tumors in nude mice. A C1P5 mAb to E6 linked to the beta-emitter 188-Rhenium ((188)Re) as utilized. Mice were treated with: (1) 200 muCi (188)Re-C1P5 alone; (2) the proteasome inhibitor MG132 alone; (3) MG132 followed by 200 muCi (188)Re-C1P5; (4) unlabeled C1P5; (5) 200 muCi (188)Re-18B7 (isotype-matching control mAb); (6) no treatment. (188)Re-C1P5 alone and in combination with MG-132 significantly retarded tumor growth compared to all the other   groups. Hence, these observations suggest that this radiopharmaceutical approach to targeting viral antigens may be effective against levels of antigen found in human tumors and thereby may have the potential for efficacy in the treatment of cervical cancer.  

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