Cytotoxic Activity of an Anti-CD56 Antibody-Drug Conjugate, ab906-PBD, in Neuroblastoma

Background:

Neuroblastoma, the most prevalent cancer during the first year of life, is an embryonal tumor believed to originate from neural crest precursor cells. Today, patients with high-risk neuroblastoma receive multimodal cytotoxic chemoradiotherapy, yet their long-term survival rate remains below 50% and surviving patients often experience significant late effects.

Given the relative paucity of effective treatment options for high-risk neuroblastoma patients, research efforts have focused on developing targeted therapies, including immunotherapies. Since anti-GD2 therapeutic antibodies first demonstrated efficacy in high-risk neuroblastoma in 2010, several other immunotherapy targets have been suggested. Among these is CD56 (neural cell adhesion molecule/NCAM), a cell adhesion molecule that is highly expressed on most neuroblastoma tumors and may contribute to neuroblastoma's metastatic potential in certain patients.

Project Goal:

The proposed project would investigate the cytotoxic potential of a novel antibody-drug conjugate (ADC) directed against CD56, ab906-PBD. ADCs containing PBD dimers have demonstrated cytotoxic activity against various tumor types including acute myeloid leukemia, renal cell carcinoma, and non-Hodgkin's lymphoma.