Cancer Stromal Targeting

Abstract

Antibody-drug conjugate (ADC) targeting tumor cells themselves was effective for hematological malignancy or breast cancer having hyper- vascularity and poor stroma. However, it was not effective for the refractory tumors such as brain tumor, scirrhous gastric cancer or pancreatic cancer. Dense stroma prevents the ADC form reaching the tumor cells within the tumor tissues. To overcome "stromal barrier", we created "CAST (Cancer stromal targeting) therapy" using ADC targeting to a tumor stroma. We have succeeded in developing anti-cancer agent (SN-38) conjugated anti-collagen 4 antibody or anti-fibrin antibody. The therapy damaged both tumor cells and tumor vasculature. Bone marrow toxicity, hepatorenal disorder or autonomatous harmful immune response was not recognized. Further evaluation of the CAST therapy is necessary for a future clinical application.