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One of the reasons pancreatic cancer is so difficult to treat is that tumors are difficult to penetrate, making it difficult to give them drugs. Researchers at Boston Children’s Hospital have devised a combination treatment designed to penetrate and penetrate pancreatic cancer cells – and they have promising evidence in mice that this approach may work.
The Boston Children’s team has developed an antibody-drug conjugate (ADC) that binds to ICAM1, a molecule on pancreatic tumor cells, and delivers a cancer-killing compound. In mouse models of pancreatic cancer, two doses of the drug shrunk tumors and prevented metastasis, the researchers reported in the journal Advanced Science.
The researchers began by screening the surface of pancreatic tumor cells for proteins that were abundant enough to serve as good binding targets. When they found ICAM1, they didn’t hesitate to choose it as their target. ICAM1 facilitates certain immune responses, and they knew from their previous research that the protein is abundant in other cancers, including melanoma and triple negative breast cancer. In fact, they reported last year that a targeted ICAM1 treatment developed at Boston Children’s was effective in mouse models of triple negative breast cancer.
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They then selected the best drug to include in their ADC by screening for compounds already used in cancer treatment. They tested four different combinations before landing on DM1, the anticancer drug used in Roche’s Kadcyla ADC for HER2-positive breast cancer.
For the mouse study, they compared their DM1-ICAM1 combo with two other treatments and a placebo over a 14-week treatment period. One of the ADCs they tested combined DM1 with Gemzar, a chemotherapy drug usually given as a first-line treatment for pancreatic cancer. ADC DM1-ICAM1 outclassed them all.
Several biotechnology companies are working on ADCs to treat pancreatic cancer, with mixed success. One, developed by MedImmune several years ago, failed in early human testing due to serious side effects. Boston Children’s researchers believe that ICAM1 is expressed at higher levels in pancreatic cancer than the drug target of MedImmune, which “may enhance the therapeutic effect and reduce side effects,” they wrote in the. study.
The Boston Children’s team developed an MRI-based imaging technique that they used to confirm the presence of ICAM1 on pancreatic tumor cells during the study. They believe the same technique could be used with their ADC to track its effectiveness over time in patients.
“The precision of our approach comes from both specific targeting and the ability to monitor that targeting with MRI,” said co-author Marsha Moses, Ph.D., director of the vascular biology program at Boston Children’s. , in a press release.
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