1. Genetic manipulation of NK cells. We are designing novel CAR and non-CAR gene constructs aimed at enhancing NK and other innate immune cell targeting of cancer cells and immunosuppressive tumor microenvironment. Major gene editing projects in our lab include: a) TCR-like (TCR-mimetic) CAR NK cells for NPM1c mutated AML b) Mesothelin CARs with secondary arming for ovarian, pancreatic and lung cancer c) STING modulation in the TME to enhance NK cell CAR function d) NK cell CAR against a novel target in myeloproliferative neoplasms e) CRISPR based gene editing for enhanced NK cell function f) Multiplex CRISPR edited iPSC derived NK cells for enhanced tumor immunotherapy g) Checkpoint targeted CARs to overcome tumor tolerance in advanced malignancies h) Novel peptide delivery system to the immune-suppressive tumor microenvironment i) Tumor associated metabolic pathway modulation j) Novel synthetic protein delivery for enhanced tumor killing
2. Development of novel cytokines for the modulation of immunosuppressive TME
3. Immune reconstitution after stem cell transplantation
4. Translation of memory-like NK cells in cancer: - AML, MDS and MPN relapsed after allogeneic transplantation. This clinical trial is currently enrolling patients (Clinicaltrials.gov ID: NCT04024761).
- MRD positive myeloma patients undergoing transplantation (collaboration with Dr. Giada Bianchi). This clinical trial is currently enrolling patients (Clinicaltrials.gov ID: NCT04634435).
- Platinum refractory head and neck cancer (collaboration with Drs. Glenn Hanna and Ravi Uppaluri). This clinical trial is currently enrolling patients (Clinicaltrials.gov ID: NCT04290546).
- Advanced kidney and bladder cancer (collaboration with Drs Toni Choueiri and Wenxin Xu). IND pending / undergoing regulatory approval. - Advanced ovarian cancer (collaboration with Drs. Ursula Matulonis and Rebecca Porter). IND pending / undergoing regulatory approval.
5. Machine learning algorithm for KIR/HLA interactions in stem cell transplantation (collaboration with Dr. John Koreth)