Anti-Cadherin 3 antibody labeled with Y-90 effectively inhibits tumor growth of non-small cell lung cancer xenograft in nude mice by radioimmunotherapy

Objectives Previous immunohistochemical study revealed Cadherin 3/P-cadherin (CDH3) is overexpressed in various human cancer, whereas normal tissues have minimal expression. This molecule is predicted as a new target for immunotherapy. We persuade whether CDH3 could be a therapeutic target and anti-CDH3 monoclonal antibody (mAb) is possible to apply for radioimmunotherapy.

Methods A human non-small cell lung cancer cell line, NCI-H358, was used for a xenograft model in nude mice. MAbs with high affinity to CDH3 positive cancer cell were selected for candidates of immunotherapy by FACS analysis. Anti-CDH3 mouse mAbs conjugated with p-SCN-Bn-DOTA were labeled with Ga-67 and injected intravenously to mice xenograft model. Organ biodistribution and tumor uptake were measured by gamma counter in each organ or tumor. For radioimmunotherapy, an antibody-DOTA conjugate labeled with Y-90 was inoculated into xenograft mice (n=8) and efficacy was evaluated by tumor size and weight.

Results An organ biodistribution study showed Ga-67 labeled mAbs reached approximately 30% ID (injected dose) /g tumor weight at 96hrs post injection. An antibody with the best tumor uptake was chosen for examining therapeutic efficacy. A mAb was labeled with Y-90 and inoculated intravenously into mice bearing average 150 sq. mm of tumor. Mice administrated with 7.4 MBq per mouse revealed almost 100% tumor growth inhibition compared with injected saline by tumor size and weight. A group bearing average 300 sq. mm of tumor has almost equal inhibition in the same dose as well. The efficacy was appeared as dose escalation at 1.85, 3.7, 5.6 or 7.4 MBq per mouse, respectively.

Conclusions This study suggests that an anti-CDH3 antibody can be a potential candidate of therapeutic agent for various cancer treatments