Malignant primary and metastatic brain tumors have no cure and are particularly difficult to target due to blood brain barrier. Stem cells have risen as a promising therapeutic carrier for brain tumor targeted delivery of therapeutics. A brain tumor tropic stem cell detects and pursues the neoplasm from afar, overcomes barriers, endures the harsh tumor microenvironment, and challenges the malignant growth of brain tumors with unwavering intent to kill. Natural tumor tropism has been shown in stem cells of various sources, including autologous mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and allogeneic neural stem cells (NSCs), preclinical studies have confirmed their potential for anti-tumor therapeutics. However, vast majority of implanted stem cells do not migrate to tumor due to lack of receptor for tumor-specific cytokines or migratory molecular machineries. To mobilize and amass sufficient number of NSCs in situ to juxtapose tumor cells for efficacious therapy, I hypothesize that gene editing of tumor-specific cytokine receptors and integrins potentiates the tumor tropism of engineered NSCs, paving the way for augmented anti-tumor efficacy. Leveraging the nascent CRISPR SAM (Clustered Regularly Interspersed Short Palindromic Repeats Synergistic Activation Mediators) technology to selectively turn on gene expressions responsible for tumor tropism, we are able to customize and augment the coordinated tumor targeting of allogeneic NSCs via gene activation of EGFR and integrinα2β1. This project defines a novel paradigm to engineer stem cells for potent therapeutic targeting customizable for various types of brain tumors.
|Effective start/end date||3/1/17 → 10/31/18|
- Elsa U. Pardee Foundation (Agmt Awarded 12/02/16)