One of the major reasons that pancreatic adenocarcinoma cancer (PDAC) has had a high mortality rate (5-yr overall survival rate ~8 %) for decades is the lack of effective and durable therapies. In this study, we describe a potent DM1-linked antibody-drug conjugate (ADC) targeting intercellular adhesion molecule 1 (ICAM1, also known as CD54), a highly overexpressed membrane protein on pancreatic cancer cells. Results demonstrate that this innovative ADC provides a significantly improved tumor-specificity and therapeutic efficacy, with IC<sub>50</sub> values that are ~2,000-fold lower than the conventional first line chemotherapeutic for PDAC, gemcitabine, while limiting drug accumulation in healthy tissues, leading to significantly reduced adverse effects. In addition, our anti-ICAM1 ADC demonstrated effectively targeted delivery into orthotopic PDAC tumors by in vivo MRI (magnetic resonance imaging) and ex vivo IVIS (in vivo imaging systems). In an orthotopic PDAC mouse model, this anti-ICAM1 ADC was well tolerated and effectively ablated PDAC tumor growth and proliferation and reduced tumor metastasis. By specific targeting to the PC tumor’s ICAM1, we have established a novel drug delivery strategy that has the potential to reduce PDAC patient death and improve patient quality of life.

Novel antibody drug conjugates for pancreatic cancer therapy

2019 Fall National Meeting

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