Dr. Theodore Nowicki's 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 previously were transgenic TCR adoptive 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. He has trained with Dr. Antoni Ribas, a worldclass expert in both of these modalities.
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.
Nowicki TS, Berent-Maoz B, Cheung-Lau G, Huang RR, Wang X, Tsoi J, Kaplan-Lefko P, Cabrera P, Tran J, Pang J, Macabali M, Garcilazo IP, Carretero IB, Kalbasi A, Cochran AJ, Grasso CS, Hu-Lieskovan S, Chmielowski B, Comin-Anduix B, Singh A, Ribas A. A Pilot Trial of the Combination of Transgenic NY-ESO-1-reactive Adoptive Cellular Therapy with Dendritic Cell Vaccination with or without Ipilimumab. Clin Cancer Res. 2019 Apr 1;25(7):2096-2108. doi: 10.1158/1078-0432.CCR-18-3496. Epub 2018 Dec 20.
Nowicki TS, Escuin-Ordinas H, Avramis E, Chmielowski B, Chodon T, Berent-Maoz B, Wang X, Kaplan-Lefko P, Yang L, Baltimore D, Economou JS, Ribas A, Comin-Anduix B. Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products. J Immunother. 2018 Jun;41(5):248-259. doi: 10.1097/CJI.0000000000000216.
Kugel CH 3rd, Douglass SM, Webster MR, Kaur A, Liu Q, Yin X, Weiss SA, Darvishian F, Al-Rohil RN, Ndoye A, Behera R, Alicea GM, Ecker BL, Fane M, Allegrezza MJ, Svoronos N, Kumar V, Wang DY, Somasundaram R, Hu-Lieskovan S, Ozgun A, Herlyn M, Conejo-Garcia JR, Gabrilovich D, Stone EL, Nowicki TS, Sosman J, Rai R, Carlino MS, Long GV, Marais R, Ribas A, Eroglu Z, Davies MA, Schilling B, Schadendorf D, Xu W, Amaravadi RK, Menzies AM, McQuade JL, Johnson DB, Osman I, Weeraratna AT. Age Correlates with Response to Anti-PD1, Reflecting Age-Related Differences in Intratumoral Effector and Regulatory T-Cell Populations. Clin Cancer Res. 2018 Nov 1;24(21):5347-5356. doi: 10.1158/1078-0432.CCR-18-1116. Epub 2018 Jun 13.
Nowicki TS, Hu-Lieskovan S, Ribas A. Mechanisms of Resistance to PD-1 and PD-L1 Blockade. Cancer J. 2018 Jan/Feb;24(1):47-53. doi: 10.1097/PPO.0000000000000303. Review.
Nowicki TS, Akiyama R, Huang RR, Shintaku IP, Wang X, Tumeh PC, Singh A, Chmielowski B, Denny C, Federman N, Ribas A. Infiltration of CD8 T Cells and Expression of PD-1 and PD-L1 in Synovial Sarcoma. Cancer Immunol Res. 2017 Feb;5(2):118-126. doi: 10.1158/2326-6066.CIR-16-0148. Epub 2016 Dec 30.