Research & Clinical Summary

The Orentas Lab is focused of the adoptive immunotherapy of cancer, focusing on pediatric leukemia, solid tumors, and CNS malignancies. We created a highly active chimeric antigen receptor T-cell (CAR-T) product against the CD22 antigen expressed on pediatric pre-B ALL, as well as a bispecific CD19/CD20 CAR, that are both currently used in clinical practice. We are continuing to improve our ability to target pre-B-ALL by the epigenetic modification CAR-T target antigens and defining mechanisms of CAR-T resistance.  The morbidity and mortality that children suffer due to pediatric solid tumors is unacceptable. Our group is creating new approaches to treating rhabdomyosarcoma, Ewing’s sarcoma, osteosarcoma, and neuroblastoma by targeting new antigens and defining how these tumors evade immunosurveillance by creating a stroma that excludes immune cells.  Our lab is also developing new ways in which T cells and NK cells can be genetically engineered with lentiviral, retroviral, as well as non-viral approaches.

Interests: Cancer, Cancer Biology

Publications

The following publications were retrieved from PubMed:

Schneider D, Xiong Y, Hu P, Wu D, Chen W, Ying T, Zhu Z, Dimitrov DS, Dropulic B, Orentas RJ,
“A Unique Human Immunoglobulin Heavy Chain Variable Domain-Only CD33 CAR for the Treatment of Acute Myeloid Leukemia.”
Frontiers in oncology 8. (2018): 539.

Majzner RG, Theruvath JL, Nellan A, Heitzeneder S, Cui Y, Mount CW, Rietberg SP, Linde MH, Xu P, Rota C, Sotillo E, Labanieh L, Lee DW, Orentas RJ, Dimitrov DS, Zhu Z, Croix BS, Delaidelli A, Sekunova A, Bonvini E, Mitra SS, Quezado MM, Majeti R, Monje M, Sorensen PHB, Maris JM, Mackall CL,
“CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors.”
Clinical cancer research : an official journal of the American Association for Cancer Research 25.8 (2019 Apr 15): 2560-2574.

Finney OC, Brakke HM, Rawlings-Rhea S, Hicks R, Doolittle D, Lopez M, Futrell RB, Orentas RJ, Li D, Gardner RA, Jensen MC,
“CD19 CAR T cell product and disease attributes predict leukemia remission durability.”
The Journal of clinical investigation 129.5 (2019 May 1): 2123-2132.

Anthony-Gonda K, Bardhi A, Ray A, Flerin N, Li M, Chen W, Ochsenbauer C, Kappes JC, Krueger W, Worden A, Schneider D, Zhu Z, Orentas R, Dimitrov DS, Goldstein H, Dropulić B,
“Multispecific anti-HIV duoCAR-T cells display broad in vitro antiviral activity and potent in vivo elimination of HIV-infected cells in a humanized mouse model.”
Science translational medicine 11.504 (2019 Aug 7): .

Bari R, Granzin M, Tsang KS, Roy A, Krueger W, Orentas R, Schneider D, Pfeifer R, Moeker N, Verhoeyen E, Dropulic B, Leung W,
“A Distinct Subset of Highly Proliferative and Lentiviral Vector (LV)-Transducible NK Cells Define a Readily Engineered Subset for Adoptive Cellular Therapy.”
Frontiers in immunology 10. (2019): 2001.

Bari R, Granzin M, Tsang KS, Roy A, Krueger W, Orentas R, Schneider D, Pfeifer R, Moeker N, Verhoeyen E, Dropulic B, Leung W,
“Corrigendum: A Distinct Subset of Highly Proliferative and Lentiviral Vector (LV)-Transducible NK Cells Define a Readily Engineered Subset for Adoptive Cellular Therapy.”
Frontiers in immunology 10. (2019): 2784.

Ravanpay AC, Gust J, Johnson AJ, Rolczynski LS, Cecchini M, Chang CA, Hoglund VJ, Mukherjee R, Vitanza NA, Orentas RJ, Jensen MC,
“EGFR806-CAR T cells selectively target a tumor-restricted EGFR epitope in glioblastoma.”
Oncotarget 10.66 (2019 Dec 17): 7080-7095.

Li D, Li N, Zhang YF, Fu H, Feng M, Schneider D, Su L, Wu X, Zhou J, Mackay S, Kramer J, Duan Z, Yang H, Kolluri A, Hummer AM, Torres MB, Zhu H, Hall MD, Luo X, Chen J, Wang Q, Abate-Daga D, Dropulic B, Hewitt SM, Orentas RJ, Greten TF, Ho M,
“Persistent Polyfunctional Chimeric Antigen Receptor T Cells That Target Glypican 3 Eliminate Orthotopic Hepatocellular Carcinomas in Mice.”
Gastroenterology 158.8 (2020 Jun): 2250-2265.e20.

Jackson Z, Roe A, Sharma AA, Lopes FBTP, Talla A, Kleinsorge-Block S, Zamborsky K, Schiavone J, Manjappa S, Schauner R, Lee G, Liu R, Caimi PF, Xiong Y, Krueger W, Worden A, Kadan M, Schneider D, Orentas R, Dropulic B, Sekaly RP, de Lima M, Wald DN, Reese JS,
“Automated Manufacture of Autologous CD19 CAR-T Cells for Treatment of Non-hodgkin Lymphoma.”
Frontiers in immunology 11. (2020): 1941.

Shah NN, Johnson BD, Schneider D, Zhu F, Szabo A, Keever-Taylor CA, Krueger W, Worden AA, Kadan MJ, Yim S, Cunningham A, Hamadani M, Fenske TS, Dropulić B, Orentas R, Hari P,
“Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose escalation and expansion trial.”
Nature medicine 26.10 (2020 Oct): 1569-1575.

Paugh BS, Baranyi L, Roy A, He HJ, Harris L, Cole KD, Artlip M, Raimund C, Langan PS, Jana S, Orentas RJ, Lin-Gibson S, Krueger W, Dropulić B,
“Reference standards for accurate validation and optimization of assays that determine integrated lentiviral vector copy number in transduced cells.”
Scientific reports 11.1 (2021 Jan 11): 389.

Schneider D, Xiong Y, Wu D, Hu P, Alabanza L, Steimle B, Mahmud H, Anthony-Gonda K, Krueger W, Zhu Z, Dimitrov DS, Orentas RJ, Dropulić B,
“Trispecific CD19-CD20-CD22-targeting duoCAR-T cells eliminate antigen-heterogeneous B cell tumors in preclinical models.”
Science translational medicine 13.586 (2021 Mar 24): .

Webster B, Xiong Y, Hu P, Wu D, Alabanza L, Orentas RJ, Dropulic B, Schneider D,
“Self-driving armored CAR-T cells overcome a suppressive milieu and eradicate CD19⁺ Raji lymphoma in preclinical models.”
Molecular therapy : the journal of the American Society of Gene Therapy . (2021 May 8): .

Zhang HF, Hughes CS, Li W, He JZ, Surdez D, El-Naggar AM, Cheng H, Prudova A, Delaidelli A, Negri GL, Li X, Orum-Madsen MS, Lizardo MM, Oo HZ, Colborne S, Shyp T, Scopim-Ribeiro R, Hammond CA, Dhez AC, Langman S, Lim JK, Kung SH, Li A, Steino A, Daugaard M, Parker SJ, Klein Geltink RI, Orentas RJ, Xu LY, Morin GB, Delattre O, Dimitrov DS, Sorensen PH,
“Proteomic screens for suppressors of anoikis identify IL1RAP as a promising surface target in Ewing sarcoma.”
Cancer discovery . (2021 May 21): .

Vitanza NA, Johnson AJ, Wilson AL, Brown C, Yokoyama JK, Künkele A, Chang CA, Rawlings-Rhea S, Huang W, Seidel K, Albert CM, Pinto N, Gust J, Finn LS, Ojemann JG, Wright J, Orentas RJ, Baldwin M, Gardner RA, Jensen MC, Park JR,
“Locoregional infusion of HER2-specific CAR T cells in children and young adults with recurrent or refractory CNS tumors: an interim analysis.”
Nature medicine . (2021 Jul 12): .