Development of therapeutic antibody enhancers through glycan cleavage in refractory cancers

Pancreatic cancer has a poor prognosis and the number of deaths from this disease is increasing dramatically. There are currently no effective treatments for pancreatic cancer, and often the anticancer drugs that are used cannot be continued over the long term due to their serious side effects. Accordingly, a new treatment approach is required. In this context, Dr Masao Nakamura is developing new drugs targeting glycans that play roles in the pathogenesis of cancers. In particular, he is focusing on chondroitin sulfate (CS), a glycosaminoglycan involved in the mechanisms of cancer invasion and metastasis. Nakamura has sought to develop drugs that control CS subtypes secreted by inflammatory cells, with the goal of developing enhancers that can increase the efficacy of anticancer drugs and therapeutic antibodies by modifying cell surface glycans that increase during cancer progression. Currently, with the exception of approximately 1% of cases with specific fusion genes, there are no therapeutic antibodies considered to be effective against most pancreatic cancers. By developing antibody enhancers that can overcome the cell resistance that prevents therapeutic antibodies from accessing their target molecules, Nakamura is striving to maximize the high specificity and affinity of these antibodies. In addition, he and his team are developing analytical methods using new approaches that will facilitate a comprehensive analysis of the changes in glycans and proteins necessary for the development of therapeutic antibody enhancers.