In vitro and in vivo targeted alpha therapy (TAT) of colorectal cancer using monoclonal antibodies c30.6 and 35A7

Effective targeted cancer therapy requires high selectivity and cytotoxicity of the labelled product. We report the preparation and testing of anticolorectal cancer monoclonal antibodies c30.6 and 35A7 (specific) and WM53 (non-specific) radioimmunoconjugates (RIC) labelled with alpha-emitting Terbium-149 and positron emitting Terbium-152 using cyclic dianhydride of diethylenetriaminepentacetic acid (DTPA) as chelator. The isotopes were produced at CERN (Geneva) and ANU (Canberra). The labeling efficiency of all RICs was >90%. Stability of the RIC was tested using DTPA challenge. We found 70- 80% of the label bound to the antibody after 1-4 half-lives of respective isotopes. The selective cytotoxicity was established using MTS Assay. It was found that only specific RIC killed the colorectal cancer cells whereas free alpha and positron emitters failed to kill any cells. The non-specific RIC also proved to be non-cytotoxic. The antibody c30.6 is chimeric and has been produced by using recombinant DNA technology. The preliminary success of TAT with this chimeric antibody opens the door for a possible clinical trial, once the in vitro and in vivo investigations are complete