Experimental Therapeutics

Program Leader: Vern Schramm, Ph.D.
Co-Program Leader: Roman Perez-Soler, M.D.

Experimental Therapeutics at the Albert Einstein Center for Cancer Research (AECC) is the programmatic home for basic and clinical investigations encompassing a broad spectrum of antineoplastic modalities. Two major areas of research in the drug-development arena are:

  1. drug design: the development of novel agents for the treatment of cancer based upon transition-state principles, chemical library screening, rationale agent design, and novel proteins.
  2. immunotherapeutics: focused on understanding the mechanisms by which tumors escape immune detection and elimination and the development of agents that reactivate the immune system.

Therapeutics developments are directed to novel targets identified in this and other AECC programs. Research in Experimental Therapeutics during the last six years has resulted in a spectrum 181 cancer-related patent filings, 21 license agreements with pharma, the formation of 13 start-up companies and the recent approval of a drug for the treatment of T-cell leukemia/lymphomas in Japan. Transition-state analogue inhibitors focused on novel targets are in the pipeline, including several that impact epigenetic processes. Based upon an understanding of the structure and function of BAX, small molecule activators of BAX, developed at AECC, induce cancer cell apoptosis and are activity in vitro and mouse xenografts while BAX inhibitors prevent the cardiotoxicity of cytotoxic and targeted anticancer agents.

A novel family of immune checkpoint co-inhibitory molecules has been identified, their expression in human cancers documented, and robust development of inhibitory antibodies is underway at AECC and in collaboration with pharma. A new technology is in development consisting of a specific antigenic recognition peptide together with stimulatory T-cell signals that expand or differentiate clinically-relevant T-cell clones with minimal impact on the general T-cell repertoire. This novel approach minimizes off-target side effects associated with current clinical immunotherapies. There are robust capabilities in protein production, small molecule and fragment screening, x-ray crystallography, NMR, and mass spectroscopy with bioinformatics and systems and computational biology support based in this program.

Members in this program take the lead in AECC shared resources. Drug development efforts are supported by a developing Chemical Synthesis Shared Resource. Disease-focused working groups continue to interact with laboratory scientists to foster translational studies. Members of this program conduct all clinical therapeutic trials at AECC. There is an active Phase I/II effort, in part related to the translation of leads in this and other programs into investigator-initiated studies by this program. AECC members play important roles in ECOG-ACRIN, NRG, GOG, COG, and the AMC. There are currently 52 members from 21 departments.

Member Joseph Sparano in the news:

Joseph A. Sparano, MD, on Early-Stage Breast Cancer: Findings on the Tumor Microenvironment from Harborside Press on Vimeo.