Experimental Therapeutics

Albert Einstein College Of Medicine, Bronx NY

Investigators

Linked publications, trials & patents

Abstract

PROJECT SUMMARY - EXPERIMENTAL THERAPEUTICS PROGRAM Experimental Therapeutics (ET) is the programmatic home for the design, preclinical development, and early clinical evaluation of a broad spectrum of new antineoplastic modalities developed within all programs, and for the conduct of all clinical therapeutic trials at AECC. There are two major areas of research in the drug- development arena: (1) drug design and preclinical development of novel agents for the treatment of cancer based upon transition-state principles, chemical library screening, rational agent design, and novel proteins; (2) new immunotherapeutics based on understanding the mechanisms by which tumors escape immune detection and elimination; and the preclinical development of agents that activate the immune system. Therapeutics developments are directed to novel targets identified in this and other programs. This research has resulted in a spectrum of IPs, the formation of several companies, and the recent approval of a drug for the treatment of T-cell leukemia/lymphomas in Japan. A number of transition-state inhibitors focused on novel targets are in the pipeline, including several that impact on 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 active in vitro and in mouse xenografts, while BAX inhibitors prevent the cardiotoxicity of cytotoxic and targeted 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 in development consists of a specific antigenic recognition peptide together with stimulatory T-cell signals that expand or differentiate clinically-relevant T-cell clones but have minimal impact on the general T-cell repertoire, thus ensuring selectivity and avoidance of the side effects of current immune checkpoint inhibitors. There are robust capabilities in protein production, small molecule and fragment screening, x-ray crystallography, NMR and mass spectrometry, with bioinformatics and systems and computational biology support based in this program and in the AECC shared resources led by members of this program. Drug development efforts are supported by a developing Chemical Synthesis shared resource. Disease-focused working groups interact with laboratory scientists to foster translational studies. There is an active Phase I/II program for early clinical evaluation of leads in this and other programs into investigator-initiated studies by this program along with an established CAR-T program one of only two in the region. AECC members play important roles in ECOG-ACRIN, NRG, GOG, COG, and the AMC. There are 52 program members from 21 departments. Current NCI funding is 2.2M (dc); total peer-reviewed funding is 5.2M (dc). There have been 981 publications since July 2013 of which 22% represent intra-programmatic, 21% inter- programmatic, and 58% collaborations with investigators at other institutions.