Theodore Nowicki
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Email Address:
tnowicki@mednet.ucla.edu
Assistant Professor & Clinical Instructor, Pediatrics-Hematology/Oncology, Microbiology, Immunology & Molecular Genetics
Dr. Theodore Scott Nowicki is a pediatric hematologist/oncologist and immunologist whose area of interest is in T-cell-based cancer immunotherapy, determining biological differences between responders and non-responders to these therapies, and using this information to further improve these cellular immunotherapeutics. The clinical paradigms with which he has been most interested are transgenic TCR adoptive cell therapy, CAR-T cell therapy, immune checkpoint inhibition via blockade of CTLA-4, PD-1, and PD-L1, and the combination of both modalities to further optimize cellular therapies.
Dr. Nowicki’s research focuses on functional DNA methylomic evolution of transgenic TCR products in clinical scenarios. This approach utilizes a multi-omic approach utilizing whole genome bisulfite sequencing, ATAC-seq, and RNA-seq in order to assess areas of DNA methylation change which are directly responsible for changes in chromatin accessibility and corresponding gene expression in aging transgenic TCR-T cells which can lose therapeutic efficacy over time. He also studies T-cell therapeutics’ functionality at the single-cell proteomic/secretomic level.
Another area of Nowicki’s ongoing research deals with the phase I clinical trial of co-administration of autologous peripheral blood stem cells expressing the NY-ESO-1 TCR and a suicide/reporter gene combined with T-cells expressing the same TCR for the treatment of metastatic NY-ESO-1-positive solid tumors. This is a unique, cutting-edge approach to cell therapy not practiced anywhere else. Furthermore, he is pursuing longitudinal translational studies on the persistence, phenotype and functionality of these transgenic cells over time, as well as stratifying the long-term performance of the cells that are ultimately derived from the hematopoietic stem cell niche over time in vivo. Long term, this novel approach of utilizing the hematopoietic stem cell niche to induce long-term persistence of transgenic T-cells has the potential to create a paradigm shift in how oncologists approach these treatment modalities for the most aggressive adult and pediatric cancers.
Dr. Nowicki earned his M.D. and Ph.D. degrees from New York Medical College, where he completed his dissertation with Dr. Jan Geliebter. He completed his residency in general pediatrics and his fellowship in pediatric hematology/oncology at UCLA Medical Center, where he was also a post-doctoral fellow in the laboratory of Dr. Antoni Ribas.
A selected list of publications:
K.M. Campbell, M. Thaker, E. Medina, A. Kalbasi, A. Singh, A. Ribas, T.S. Nowicki. Spatial profiling reveals association between WNT pathway activation and T-cell exclusion in acquired resistance of synovial sarcoma to NY-ESO-1 transgenic T-cell therapy. Journal for ImmunoTherapy of Cancer, 2022;10(3):e004190. PMCID: Not available.
T.S. Nowicki*, C. Farrell, M. Morselli, L. Rubbi, K. Campbell, M. Macabali, B. Berent-Maoz, B. Comin-Anduix, M. Pellegrini, A. Ribas. Epigenetic Suppression of Transgenic T-cell Receptor Expression via Gamma-Retroviral Vector Methylation in Adoptive Cell Transfer Therapy. Cancer Discovery. 2020; 10(11):1645-1653. PMCID: PMC7641915.
* denotes both lead author and sole corresponding author
T.S. Nowicki, B. Berent-Maoz, G. Cheung-Lau, R. Huang, X. Wang, J. Tsoi, P. Kaplan-Lefko, P. Cabrera, J. Tran, J. Pang, M. Macabali, I. Perez Garcilazo, I. Baselga Carretero, A. Kalbasi, A.J. Cochran, C.S. Grasso, S. Hu-Lieskovan, B. Chmielowski, B. Comin-Anduix, A. Singh, A. Ribas. A Pilot Trial of the Combination of Transgenic NY-ESO-1-reactive Adoptive Cellular Therapy with Dendritic Cell Vaccination With or Without Ipilimumab. Clinical Cancer Research. 2019; 25(7):2096-2108. PMCID: PMC6445780.
T.S. Nowicki, H. Escuin-Ordinas, E. Avramis, B. Chmielowski, T. Chodon, B. Berent-Maoz, X. Wang, P. Kaplan-Lefko, L. Yang, D. Baltimore, J.S. Economou, A. Ribas, B. Comin-Anduix. Characterization of post-infusion phenotypic differences in fresh versus cryopreserved TCR engineered adoptive cell therapy products. Journal of Immunotherapy. 2018; 41(5):248-259. PMCID: PMC5959255.
T.S. Nowicki, S. Hu-Lieskoven, A. Ribas. Mechanisms of Resistance to PD-1 and PD-L1 blockade. The Cancer Journal: The Journal of Principles & Practice of Oncology. 2018; 24(1):47-53. PMCID: PMC5785093.
T.S. Nowicki, R. Akiyama, R.R. Huong, I.P. Shintaku, X. Wang, P.C. Tumeh, A. Singh, B. Chmielowski, C. Denny, N. Federman, A. Ribas. Infiltration of CD8 T cells and expression of PD-1 and PD-L1 in synovial sarcoma. Cancer Immunology Research. 2017; 5(2):118-126. PMCID: PMC5290092.
Awards and Memberships
Grant Review Committees:
Ad Hoc Member – Transplantation, Tolerance, and Tumor Immunology Study Section, NIH
Clinical Research Committee – Biomarker Project Award, Cancer Research UK
Science Committee – Cancer Immunology Project Award, Cancer Research UK
Ad Hoc Grant Reviewer – Dutch Cancer Society (KWF Kankerbestrijding)
Professional Memberships:
American Association for Cancer Research (AACR)
American Society of Gene and Cell Therapy (ASGCT)
Children’s Oncology Group (COG)
American Academy of Pediatrics (AAP)
American Society of Clinical Oncology (ASCO)
American Society of Hematology (ASH)
Society for ImmunoTherapy of Cancer (SITC)
Journal Review Experience:
Reviewer, Cancer Discovery
Reviewer, Journal of the National Cancer Institute
Reviewer, Cancer Immunology Research
Reviewer, Nature Immunology
Reviewer, Molecular Therapy
Reviewer, Trends in Immunology
Reviewer, OncoImmunology
Reviewer, European Journal of Immunology
Reviewer, Cancer Immunology, Immunotherapy
Reviewer, The EMBO Journal
Reviewer, Journal of Experimental Medicine
Reviewer, Clinical Cancer Research
Reviewer, BMC Cancer
Reviewer, Bioinformatics
Reviewer, Pediatric Hematology and Oncology