Fall 2024
Dr. Matthew Wolf, PhD, NIH National Cancer Institute (NCI) (LINK)
Friday, 08/30/2024
12:10 PM – 1:00 PM (Seminar)
1:00 PM – 2:00 PM (Student and faculty interaction)
Chemistry Bldg. room G8 / G9
Title: “Development of an extracellular matrix scaffold-assisted therapeutic cancer vaccine: at the crossroads of biomaterials, tissue engineering, and immunology.”
Abstract:
Injectable scaffold delivery is an immune engineering strategy to enhance the efficacy of cancer vaccine immunotherapy. The type of biomaterial scaffold affects both vaccine release kinetics and immune stimulation via the scaffold host response. Extracellular matrix (ECM) scaffolds prepared from decellularized tissues initiate an alternative inflammatory response following implantation, which facilitates wound healing following tumor resection and promotes local cancer immune surveillance. Here, we engineered an ECM scaffold-assisted therapeutic cancer vaccine that maintained an immune microenvironment consistent with tissue repair. We screened immune adjuvants to formulate a decellularized small intestinal submucosa (SIS) ECM scaffold cancer vaccine. We found that the STING pathway adjuvant CDA was the most potent cytotoxic inducer with SIS-ECM scaffold delivery and did not diminish hallmark signaling pathways associated with wound healing such including IL4. SIS scaffold delivery enhanced therapeutic vaccine efficacy, curing 50-75% of established EG.7 tumors, compared to soluble components alone (0% cured). SIS-ECM scaffold assisted vaccination extended antigen exposure, was mediated by CD8+ cytotoxic T cells, and generated long-term anti-tumor memory at least 7 months post-vaccination in both young and mature-aged mice. We then translated this approach to a novel Surgical Genetic Mouse Model Allograft (Surgi-GEMMA) of tumor resection and ECM-vaccine implantation. CDK4(R24C)-Hgf-Tg melanoma allograft tumors had >90% recurrence with surgical resection or neoadjuvant immunotherapy; however, we found recurrence rates dropped to 45% when immediately implanted with an FDA approved ECM mesh infused cancer vaccine. This study shows that an ECM scaffold is a promising delivery system to enhance cancer vaccine efficacy while being orthogonal to characteristics of pro-healing immune hallmarks necessary to tissue engineering applications.
Speaker Bio:
Dr. Matthew Wolf, PhD, is a Stadtman Investigator in the NIH National Cancer Institute (NCI) where he is head of the Cancer Biomaterials Engineering Section. Dr. Wolf investigates immunomodulatory biomaterials to enhance the efficacy and development of next-generation cancer immunotherapies to treat solid tumors. His lab integrates tissue engineering & biomaterials science with immune oncology using biomaterial scaffolds to deliver signaling cues that direct immune function. This includes applications as immune cell activating scaffolds for cancer vaccine delivery, and 3D tumor microenvironment models in-a-dish. He showed that alternative Type 2 immune induction by biologic scaffolds can restrict tumor growth and be leveraged to prime cytotoxic T cells in a therapeutic cancer vaccine. Dr. Wolf earned his PhD in Bioengineering at the University of Pittsburgh McGowan Institute for Regenerative Medicine and conducted his postdoctoral work at the Johns Hopkins University Translational Tissue Engineering Center and Bloomberg~Kimmel Institute for Immunotherapy before starting his lab at the NCI as a tenure track investigator. He was the recipient of the Immune Modulation and Engineering Symposium (IMES) Early Career Investigator Award.
Spring 2024
01.12.24 Faculty Prof. Alisa Clyne, UMD https://bioe.umd.edu/clark/faculty/1011/Alisa-Morss-Clyne
01.19.24 No seminar
01.26.24 Faculty Dr. Tagbo Niepa, CMU https://www.cheme.engineering.cmu.edu/directory/bios/niepa-tagbo.html
01.31.24 No Seminar
02.02.24 University Holiday
02.09.24 Faculty Dr. Mercedes Taylor, UMD https://chem.umd.edu/people/mercedes-taylor
02.28.24 Prof. Shis-Yuan Liu, BC https://www.bc.edu/bc-web/schools/morrissey/departments/chemistry/people/faculty-directory/shih-yuan-liu.html
03.08.24 University Holiday
03.22.24 Prof. Geoffrey Hutchinson, UPitt https://www.chem.pitt.edu/person/geoffrey-hutchison
04.12.24 Dr. Gregg Duncan, UMD https://bioe.umd.edu/clark/faculty/797/Gregg-Duncan
04.26.24 Dr. Ivan Dmochowski, UPenn https://www.chem.upenn.edu/profile/ivan-j-dmochowski
DEPARTMENT OF CHEMISTRY
525 College Street, NW / Washington, D.C. 20059 / Phone: 202-806-6900