Human Immunologic Monitoring and cGMP

NIH RePORTER · NIH · P30 · $4,735 · view on reporter.nih.gov ↗

Abstract

ABSTRACT The main purpose of the Human Immunologic Monitoring and Current Good Manufacturing Practice (HIM- cGMP) Facility is to provide support to investigators at the University of Chicago Medicine Comprehensive Cancer Center (UCCCC) who conduct immunotherapy clinical trials through preparing vaccines and other novel immunotherapies for patient administration, and by evaluating various immunologic endpoints from patient samples. The HIM Subcore was initiated in 1999 as a Developing Core and has been under continuous direction by Thomas Gajewski, MD, PhD, since that time. In 2002, the HIM Core Facility became a full CCSG Core. The cGMP Subcore was initiated as a UCCCC Developing Core in 2001 and has been under continuous direction by Amittha Wickrema, PhD, since its inception. In 2011, the HIM Facility formally merged with the cGMP Facility, which streamlined the interface between the two components, including shared technical staff. With the increasing role of immunotherapy in the portfolio of cancer therapeutics, the activities of the HIM- cGMP Facilty are vital for the scientific investigation of novel agen and have been expanding rapidly. In addition to providing standard assays to measure immunologic endpoints and to monitor biologic effects of other pharmacologic agents using lymphocytes as a surrogate tissue, the Facilty has integrated new technologies to facilitate the study of novel biomarkers in patients. For example, UCCCC investigators first described the T cell-inflamed/non-inflamed tumor microenvironment gene expression profile that has been explored as a predictive biomarker for response to checkpoint blockade therapy. Understanding the mechanism by which this spontaneous anti-tumor T cell response develops in some patients, and the mechanism by which immune exclusion occurs in the remaining patients, is highlighting mechanisms of resistance and new therapeutic targets. The HIM-cGMP Facility has integrated new technologies that are facilitating identification of these mechanisms. The Facility recently purchased a Nanostring nCounter instrument, which enables gene expression profiling from formalin-fixed paraffin-embedded (FFPE) tissue, as well as an RNAscope system, for visualizing in situ expression of specific mRNAs. In addition, new protocols for banking stool for microbiota sequencing, blood for germline DNA analysis, and serum for specialized biochemical assays have been developed. Thus, in addition to standard immunologic assays, the HIM-cGMP Facility is facilitating the analysis of multidimensional correlations between mutational patterns in the tumor, germline genetic polymorphisms, and the composition of intestinal micriobiota, all with respect to immunotherapy clinical outcome.

Key facts

NIH application ID
10178296
Project number
3P30CA014599-45S2
Recipient
UNIVERSITY OF CHICAGO
Principal Investigator
THOMAS F GAJEWSKI
Activity code
P30
Funding institute
NIH
Fiscal year
2020
Award amount
$4,735
Award type
3
Project period
— → —