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A Rationally Designed ICAM1 Antibody Drug Conjugate for Pancreatic Cancer
Jing Huang1,2, Agoston T Agoston3, Peng Guo1,2
1Vascular Biology Program Boston Children's Hospital Boston MA 02115 USA.
Abstract:
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.
Insights
A new antibody-drug conjugate (ADC) targets ICAM1 for pancreatic cancer (PC) treatment. This precision medicine approach, combined with MRI imaging, shows potent tumor regression and potential for patient selection.
Area of Science:
- Oncology
- Biotechnology
- Medical Imaging
Background:
- Pancreatic cancer (PC) has a poor prognosis with less than 8% 5-year survival due to limited effective treatments.
- There is a critical need for novel therapeutic strategies and precision medicine approaches for PC.
- ICAM1 is identified as a potential therapeutic target due to its overexpression on PC cells.
Purpose of the Study:
- To develop a novel precision medicine approach for pancreatic cancer treatment using an ICAM1-targeting antibody-drug conjugate (ADC).
- To establish a magnetic resonance imaging (MRI)-based molecular imaging method for noninvasive evaluation of ICAM1 ADC therapy efficacy.
- To investigate the potential of ICAM1 as a biomarker for patient selection in PC treatment.
Main Methods:
- Development of a rationally designed ICAM1 antibody-drug conjugate (ADC) with an optimized chemical linker and cytotoxic payload.
- In vivo evaluation of the ICAM1 ADC in an orthotopic pancreatic cancer mouse model.
- Development of an MRI-based molecular imaging approach to map tumoral ICAM1 expression.
Main Results:
- ICAM1 is differentially overexpressed on human PC cells with restricted expression in normal tissues.
- The developed ICAM1 ADC selectively targets and recognizes PC tumors in vivo.
- Potent and durable tumor regression was observed in an orthotopic PC mouse model treated with the ICAM1 ADC.
- The MRI-based imaging approach successfully mapped tumoral ICAM1 expression noninvasively.
Conclusions:
- The study presents a promising ICAM1 antibody-drug conjugate (ADC) for pancreatic cancer therapy.
- An MRI-based molecular imaging approach can noninvasively assess ICAM1 expression for potential patient stratification.
- This precision medicine strategy offers a potential new avenue for addressing the unmet need in pancreatic cancer care.
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