Boosting Chimeric Antigen Receptor T Cell Therapy via a Synthetic Vaccine
Event details
| Date | 19.09.2023 |
| Hour | 14:00 › 15:00 |
| 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:
Zoom link for attending remotely: https://epfl.zoom.us/j/64497520587
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)
- BS (Biosciences and Bioengineering), Shandong Normal University, China, 2008
- PhD (Molecular, Cell and Cancer Biology), University of Massachusetts Medical School, 2016
- Specialty Certification
- Postdoctoral Fellow, Immune Engineering, Howard Hughes Medical Institute, Massachusetts Institute of Technology, 2016-2021
- 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
- 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)