Open AccessA Rationally Designed ICAM1 Antibody Drug Conjugate for Pancreatic Cancer
Author(s) -
Huang Jing,
Agoston Agoston T.,
Guo Peng,
Moses Marsha A.
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202002852
Subject(s) - pancreatic cancer , conjugate , antibody drug conjugate , in vivo , magnetic resonance imaging , medicine , cancer research , cancer , drug , antibody , linker , monoclonal antibody , pathology , pharmacology , biology , immunology , computer science , radiology , microbiology and biotechnology , mathematical analysis , mathematics , operating system
Outcomes for pancreatic cancer (PC) patients remain strikingly poor with a 5‐year survival of less than 8% due to the lack of effective treatment modalities. Here, a novel precision medicine approach for PC treatment is developed, which is composed of a rationally designed tumor‐targeting ICAM1 antibody‐drug conjugate (ADC) with optimized chemical linker and cytotoxic payload, complemented with a magnetic resonance imaging (MRI)‐based molecular imaging approach to noninvasively evaluate the efficiency of ICAM1 ADC therapy. It is shown that ICAM1 is differentially overexpressed on the surface of human PC cells with restricted expression in normal tissues, enabling ICAM1 antibody to selectively recognize and target PC tumors in vivo. It is further demonstrated that the developed ICAM1 ADC induces potent and durable tumor regression in an orthotopic PC mouse model. To build a precision medicine, an MRI‐based molecular imaging approach is developed that noninvasively maps the tumoral ICAM1 expression that can be potentially used to identify ICAM1‐overexpressing PC patients. Collectively, this study establishes a strong foundation for the development of a promising ADC to address the critical need in the PC patient care.