Boosting Chimeric Antigen Receptor T Cell Therapy via a Synthetic Vaccine

Thumbnail

Event details

Date 19.09.2023
Hour 14:0015:00
Speaker Prof. Leyuan Ma, University of Pennsylvania, Philadelphia, PA (USA)
Location Online
Category Conferences - Seminars
Event Language English
BIOENGINEERING SEMINAR
 
Abstract:
Chimeric Antigen Receptor T cells (CAR T) are effective in hematologic malignancies, but strategies to augment their therapeutic impact especially in solid tumors are still needed. Here we demonstrate an approach to enhance CAR T function by vaccine-boosting donor cells through their chimeric receptor directly in vivo. Amphiphile CAR T ligand vaccine (amph-vax) were designed, which on injection trafficked to lymph nodes, decorated the surfaces of antigen presenting cells, and primed CAR T cells in the native lymph node microenvironment. Amph-vax boosting triggered massive CAR T expansion, increased donor cell polyfunctionality, and enhanced anti-tumor efficacy in multiple immunocompetent tumor models. Unexpectedly, in vivo vaccine boosting of CAR T cells triggered engagement of the endogenous immune system to circumvent antigen-negative tumor escape and more effectively treat established tumors with pre-existing antigenic heterogeneity. This process was accompanied by shifts in CAR T metabolism toward oxidative phosphorylation in CAR T cells and was critically dependent on CAR T-derived IFN-γ. Thus, vaccine boosting provides a clinically-translatable strategy to enhance CAR T cell therapy against solid tumors.

Bio:
Position:
  • Assistant Professor of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (USA)
Education:
  • BS (Biosciences and Bioengineering), Shandong Normal University, China, 2008
  • PhD (Molecular, Cell and Cancer Biology), University of Massachusetts Medical School, 2016
  • Specialty Certification
Postgraduate Training:
  • Postdoctoral Fellow, Immune Engineering, Howard Hughes Medical Institute, Massachusetts Institute of Technology, 2016-2021
Awards and Honors:
  • Excellent Student, Shandong Normal University, 2005
  • First Class Award, Shandong Normal University, 2005
  • Outstanding Bachelor’s Degree Thesis, Shandong Province, 2008
  • Sigma Xi Grant-in-Aid of Research, 2014
  • Dean’s Award for most insightful mid-thesis research, 2015
  • Chinese Government Award for Outstanding Self-Financed Students Abroad, 2016
  • Koch Institute Marlena Felter Bradford Research Travel Fellowship, 2019
  • American Cancer Society Postdoctoral Fellowship Award, 2019
  • NIAID New Innovators Awards/DP2, 2022-2027
  • Mesothelioma Research Grant Award, 2023
  • The Ben & Catherine Ivy Foundation Translational Adult Glioma Award, 2023
  • Melanoma research Alliance Young Investigator Award, 2023
  • Neuroblastoma neoantigen vaccine U01 (co-I), 2023
  • W.W. Smith Charitable Trust award, 2023
Memberships and Professional Organizations:
  • Sigma Xi, The Scientific Research Society, 2014 - 2018
  • Biomedical Engineering Society (BMES), 2018 - Present
  • American Society of Gene & Cell Therapy, 2022 - Present
  • American Association for Cancer Research, 2023 - Present
  • Society for Immunotherapy of Cancer, 2023 - Present


Zoom link for attending remotely: https://epfl.zoom.us/j/64497520587
 

Practical information

  • Informed public
  • Free

Organizer

Contact

  • Li Tang, Ph.D.
    Associate Professor
    Institute of Bioengineering (IBI) / Institute of Materials (IMX)
    École polytechnique fédérale de Lausanne (EPFL)

Share