Project: Cancer immunotherapy: rejuvenation of anti-cancer response by immune checkpoint blockade using novel multifunctional nanoparticle to block CTLA-4 and eliminate ICER
Project Acronym: TEIGER
Duration: 2021-2023
Coordinator Name: prof. Ing. Zdeněk SOFER, Ph.D.
Coordinator Institute: University of Chemistry and Technology, Prague, Czech Republic
Partners:
- Josef Bodor, NanoSYS Biologics, Czech Republic
- Frank Pavan, V-Nano, France
- Oscar Lee, National Yang-Ming University, Taiwan
- Yi-Shiuan Liu, Chang Gung University, Taiwan
Abstract:
Checkpoint blockade immunotherapies work by inhibiting pathways that keep the duration and strength of the immune system in check. To treat cancer by targeting the immune system instead of the tumor itself is an attractive approach since fighting a tumor directly requires depletion of all malignant cells. Even a small number of surviving tumor cells can induce recurrence, thus, traditional anticancer drugs need to reach billions of cells. On the contrary, for cancer immunotherapy, it is more realistic to achieve the activation of several thousands of leukocytes sufficient to induce a potent anticancer response.
Our strategy for removal of immune tolerance is to elicit antitumor immunity in several thousands of T cells using mesoporous silica nanoparticle targeting potent immune checkpoint inhibitors irrespective of their cellular localization; such as inducible cyclic adenosine monophosphate early repressor (ICER) in the nucleus and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) on T cell’s surface.
In the project, we aim to elicit antitumor immunity against melanoma via targeting ICER in CTLA-4 positive T cells using MSNs loaded with anti-ICER small interfering RNA decorated with oligopeptides spanning specific paratopes trapping CTLA-4. Importantly, these circumvent regulatory T (Treg) cell’s ability to affect the potency of antigen-presenting cells (APCs) to activate tumor-specific T cells.