Quantitative Profiling of the Intrinsic Pathway of Apoptosis in Tumor Tissue using Myriad RBM’s Multiplex ApoptosisMAP

Regulators of apoptotic cell death are potentially valuable targets for oncology and autoimmune disease. Several promising mechanism-based compounds that directly target the molecular components of apoptosis pathways are in clinical development. It is well known that inhibition of apoptosis occurs in most cancers and can occur by a variety of methods such up regulation of anti-apoptotic factors. Until now, profiling the key components of apoptosis has been limited by the laborious and semi-quantitative method of IP-western blot which is not amenable to multiplexing and is ill suited for clinical studies from limited sample amounts.

In this webinar, Dr. Eisinger will describe the development and validation of a multiplex panel of biomarkers for quantifying the commitment, onset, and induction of apoptosis by the intrinsic pathway in tumor tissue samples. A Q&A with the audience will follow the main presentation.

Fourteen bead-based immunoassays for proteins associated with apoptosis were developed on Myriad RBM’s Multi-Analyte Profile (MAP®) platform which is based on Luminex® xMAP technology. All assays were confirmed by IP-western with the same antibody pairs used in the bead-based sandwich assays. The assays were manufactured as 3 panels: Panel 1 (BAK, BAX, Lamin B (intact +45kDa) & SMAC); Panel 2 (BAD, BAX/BCL-2 heterodimer, BCL-xl, BIM & Mcl-1); and Panel 3 (Active Caspase-3, BCL-xl/BAK heterodimer, MCL-1/BAK heterodimer, pBAD & Survivin) and validated for precision, linearity and accuracy for use with tumor biopsies, cell lysates and tissue lysates. The quantitative assays were more sensitive than IP-westerns.

Quantifying apoptotic biomarkers in clinical trials will support the pharmacodynamic action of investigational agents with companion diagnostic implications for identifying patients most likely to respond to a particular apoptosis inducer or other chemotherapeutic regimes.

Speaker

Dominic Eisinger, PhD, Director of Strategic Development, Myriad RBM

Dominic Eisinger, PhD, currently serves as the Director of Strategic Development for Myriad RBM as part of the business and scientific management team. Prior to joining Myriad RBM he was President of Multiplex Biosciences, a multiplex immunoassay development and manufacturing company. Dr. Eisinger has also held previous management positions in R&D related to multiplex immunoassay development, molecular biology and tumor vaccine antigen discovery. He has over 17 years industry experience in various scientific and commercialization roles and is a noted international authority on protein arrays.

A native of New York State, Dr. Eisinger completed his undergraduate degree from Cornell University in Biochemistry. He is trained as cellular and molecular biologist and received his PhD from the University of Vermont in stem cell differentiation before completing post-doctoral training at Dartmouth Medical School in the field of protein synthesis regulation.

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