On November 3, a team of scientists from Boston Children's Hospital reported a new progress in the treatment of pancreatic cancer in Advanced Science. Their preclinical studies have shown that using a highly selective and potent antibody-drug conjugate (ADC) can significantly and lastingly regress the tumors in mice.
Why pancreatic cancer is so difficult to treat? On the one hand, pancreatic tumors are poorly vascularized, so it is difficult to deliver drugs to the tumor, on the other hand, unlike other cancers, pancreatic tumor cells are encased in a "protective layer" composed of stromal cells and their secreted intercellular matrix.
"It is difficult to get drugs into these tumors, we have developed a new therapy (chemo-immunotherapy agent) that can selectively identify and penetrate pancreatic tumors better than other therapies." explained Dr. Marsha Moses , the leader of this new research.
To be specific, Dr. Moses' team has developed an antibody-drug conjugates targeting ICAM1. ADC is a new type of targeted drugs consisting of "monoclonal antibodies, cytotoxic drugs, and linkers that connect the two." Because antibodies are targeted (recognizing the surface antigens of cancer cells), they can selectively "transport" cytotoxic molecules directly to tumor cells, performing anticancer functions without affecting healthy cells.
Dr. Peng Guo, who participated in the study, explained: “The size of ADC is similar to the size of a single antibody. Due to small diameter, these drugs are able to penetrate the 'protective layer' and reach pancreatic cancer cells better than other innovative therapies, such as T-cell immunotherapy and nano-drugs.”
Then, the research team randomly grouped the mice carrying pancreatic tumors and each group would be treated with one of the four therapies : 1) DM1-ICAM1 antibody-drug conjugates, 2) DM1 conjugated a non-targeting antibody, 3) gemcitabine (a first-line chemotherapy drug for pancreatic cancer), and 4) PBS.
DM1-ICAM1 antibody-drug conjugates therapy also effectively inhibited the metastasis of multiple organs (including lung, liver, spleen, etc.). In addition, the toxicity of DM1-ICAM1 antibody-drug conjugates was not observed.
Dr. Moses said: “Although other ADCs have been tested in pancreatic cancer, none of them have shown sufficient efficacy in the clinic, and they can cause off-target toxicity. Our approach is expected to achieve greater precision through specific targeting and effective monitoring.” It is learned that the research team will carry out further research in the future, hoping to promote this innovative therapy into the clinical development stage.
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 Jing Huang et al. A Rationally Designed ICAM1 Antibody Drug Conjugate for Pancreatic Cancer. Advanced Science(2020)
 Precision chemo-immunotherapy for pancreatic cancer? (Resource：Children's Hospital Boston)
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