RATIONAL DESIGN OF NOVEL NANO-SIZED DELIVERY SYSTEMS FOR IMMUNOTHERAPIES
Our research is currently focused on the pharmacological aspects of a multidisciplinary project within the frontier of cancer immunotherapy where nanotechnology, immunology, chemical biology, biotechnology and animal modeling will provide the rationale for novel anticancer treatments. This approach is based on the design of precision nanomedicines that will interfere within tumor-host interactions and stimulate the immune system to attack the tumor cells. We are synthesizing PLGA-based nanovaccines targeting the dendritic cells to activate T cells against primary and secondary brain neoplasms such as glioblastoma, melanoma brain metastases and breast cancer brain metastases. Another immunotherapy approach tagging heteroaryl chemotherapeutic drug molecules with a ketone functional group and employing it for Antibody-Drug Conjugates (ADC) applications was recently published. This project is the basis for an ERC Advanced grant awarded to our lab in 2019-2024. Based on this project, we signed a contract with Merck Global Healthcare in collaboration with Prof. Doron Shabat.
Internalization of mannosylated nanovaccines (green) into dendritic cells (Membrane- Red; Nucleus- Blue)
Inhibition of PD1 expression in tumors following combination therapy with our nanovaccine and immune checkpoint inhibitors (left panel - control; right panel - nanovaccine + anti-PD-1).
Conniot J*, Scomparin A*, et al. (Satchi-Fainaro R*, Florindo H*), Ibrutinib-disabled immunosuppressive microenvironment sensitizes melanoma to PD-1/OX40 immune checkpoint modulators following dendritic cell-targeted nano-vaccines, Nature Nanotechnology, 14(9):891-901 (2019). *Corresponding authors. [PDF] [PubMed]
Gnaim S, et al.(Satchi-Fainaro R*, Shabat D*), Tagging the Untaggable: A Difluoroalkyl-Sulfinate Ketone-Based Reagent for Direct C-H Functionalization of Bioactive Heteroarenes, Bioconjugate Chemistry, 27(9):1965-71 (2016). *Corresponding authors. [PDF] [PubMed]
Zafir-Lavie I, et al. (Satchi-Fainaro R), Successful gene therapy obtained by fibroblasts expressing anti-HER2 antibody for HER2-positive breast cancer brain metastases, Journal of Controlled Release, 291:80-89 (2018). [PDF] [PubMed]