Event Title

Optimization of Targeted Cancer Therapy: BH3-mimetic Antibody-Drug Conjugates

Presenter Information

Jennifer Feigin, Oberlin College

Location

Science Center, Bent Corridor

Start Date

10-27-2017 6:40 PM

End Date

10-27-2017 7:20 PM

Research Program

Novartis Institutes for Biomedical Research

Poster Number

30

Abstract

The BCL-2 family of proteins consist of pro-apoptotic and pro-survival molecules. Pro-survival proteins, MCL-1 and BCL-xL, bind pro-apoptotic BH3-only and BAX/BAK proteins, preventing them from initiating apoptosis. Over expression of pro-survival proteins and resistance to apoptosis is a hallmark of many cancers. MCL-1 and BCL-xL inhibitors are potential therapeutic interventions that directly target pro-survival BCL-2 family proteins. This study assesses the cytotoxicity of different Antibody-Drug Conjugates & small molecule inhibitors at varying concentrations on different cell populations and assesses the smallmolecule drug's mechanism of action. Ultimately, heme and solid tumor lines are sensitive to BCL-xL and MCL1 inhibitors in vitro and cell lines that exhibit sensitivity to inhibition of BCL-2 pro-survival proteins are good potential candidates to test MCLIi and BCL-xLi ADCs targeting CD-33, PCAD, EGFR. The Initial screen with 293T cells shows the best fusion protein pairs are LgBiT-BCL-xL + SmBiT-BAK, LgBiT-MCL1 + SmBiT-BAK.

Major

Biology; History

Project Mentor(s)

Tony D'Alessio and Katherine Seiss, Novartis Institutes for Biomedical Research

This document is currently not available here.

Share

COinS
 
Oct 27th, 6:40 PM Oct 27th, 7:20 PM

Optimization of Targeted Cancer Therapy: BH3-mimetic Antibody-Drug Conjugates

Science Center, Bent Corridor

The BCL-2 family of proteins consist of pro-apoptotic and pro-survival molecules. Pro-survival proteins, MCL-1 and BCL-xL, bind pro-apoptotic BH3-only and BAX/BAK proteins, preventing them from initiating apoptosis. Over expression of pro-survival proteins and resistance to apoptosis is a hallmark of many cancers. MCL-1 and BCL-xL inhibitors are potential therapeutic interventions that directly target pro-survival BCL-2 family proteins. This study assesses the cytotoxicity of different Antibody-Drug Conjugates & small molecule inhibitors at varying concentrations on different cell populations and assesses the smallmolecule drug's mechanism of action. Ultimately, heme and solid tumor lines are sensitive to BCL-xL and MCL1 inhibitors in vitro and cell lines that exhibit sensitivity to inhibition of BCL-2 pro-survival proteins are good potential candidates to test MCLIi and BCL-xLi ADCs targeting CD-33, PCAD, EGFR. The Initial screen with 293T cells shows the best fusion protein pairs are LgBiT-BCL-xL + SmBiT-BAK, LgBiT-MCL1 + SmBiT-BAK.