Antibody drug conjugates (ADCs) are an exciting class of targeted prodrugs that combine the specific ligand binding and long circulation times of antibodies with the oncocidal properties of advanced chemotherapeutics. When compared to traditional chemotherapy, ADCs deliver more potent cytotoxins to specific cell types that express a target antigen such as HER2, ideally sparing healthy tissue from off-target toxicity. HER2 targeted ADCs such as Kadcyla™ are limited, however, by slow trafficking of bound ADCs to the lysosome where free drugs must be released to achieve cytotoxicity. This presentation outlines how the efficacy of HER2 directed ADCs can be enhanced by co-treating with a small molecule drug that inhibits HER2s critical chaperone thus “unlocking” HER2+ cancer cells by promoting internalization and lysosomal degradation of HER2-ADC adducts.Increasing the percentage of ADC payload that reaches the lysosome significantly reduces the dose required for efficacy, further reducing the risk to healthy tissues. <br/>

Enhancing cytotoxicity of antibody drug conjugates through co-administration of a potentiating antibody conjugate in an ovarian cancer model

2019 Fall National Meeting

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