Abstract

Background

ADCs form a therapeutic class that has demonstrated immense potential for transformative clinical responses in several types of cancers. Due to their complexity, however, predicting clinical properties remains a challenge. The mAb, linker, and payload all need to be optimized for a particular tumor target, indication, and patient population.. More importantly, traditional approaches can be misleading when considered in isolation, and several notable clinical ADC failures have been reported in recent years.

Abstract

Background

• Off-target hematotoxicity has been reported in the clinic for many antibody-drug conjugates (ADCs); toxicity can limit the maximum tolerated dose in the clinic.
• A mechanistic model of hematopoiesis was developed to describe thrombocytopenia post Trastuzumab-emtansine (T-DM1) administration, but could be generalized to other hematopoietic diseases and other therapeutics.
• Combining efficacy (see our other poster) and toxicity models allows us to explore common therapeut

Poster Abstract

Background and Aim

Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable success in treating various leukemias and lymphomas. CARs are engineered to redirect T cells to specific antigens. [1]

CAR-T PK behavior is distinct from other therapies due to its "living" nature; it is characterized by an exponential expansion, fast initial decline (contraction), and slow long-term decline (persistence). [2]