Combating Recalcitrant Cancer Types Through Rational Engineering of Antibody-Drug Conjugates
Abstract
In aim 1 high-throughput genomics screening will be used to uncover genes that, when overexpressed, induce CD276 expression in cells. In aim 2, we will develop next generation CD276 ADCs with enhanced cell killing activity and an improved therapeutic index.Enhancements will be introduced to our ADC to prevent Fc receptor binding, without decreasing ADC stability. Site-directed conjugation will also be used to create ADCs that are less prone to aggregation and more stable in the circulation. In aim 3, we will create a new amanitin-based ADC for targeted killing of pancreatic cancers that are intrinsically resistant to PBD. The new ADC will be engineered site specifically with additional modifications to improve ADC stability. The specificity of our improved ADCs will be rigorously monitored by comparing activity in CD276 wildtype (WT)and knockout (KO) cell lines and CD276 WT and KO mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2021
- Accession Number
- AD1228210
Entities
People
- James Dunleavey
Organizations
- Geneva Foundation