Stephan Grupp Laboratory

Led by Stephan Grupp MD, PhD, researchers in the Grupp Laboratory are focused on developing new molecular-based targeted cancer treatments and cell-based immunotherapies to treat leukemia and solid tumors. The ultimate goal of the work conducted in this laboratory is to identify and develop advanced cancer treatments that are less toxic than existing therapies and can be used to treat children with high-risk malignancies.

Selected Publications

2020

Singh N, Lee YG, Shestova O, Ravikumar P, Hayer KE, Hong SJ, Lu XM, Pajarillo R, Agarwal S, Kuramitsu S, Orlando EJ, Mueller KT, Good CR, Berger SL, Shalem O, Weitzman MD, Frey NV, Maude SL, Grupp SA, June CH, Gill S, Ruella M. 2020. Impaired Death Receptor Signaling in Leukemia Causes Antigen-Independent Resistance by Inducing CAR T-cell Dysfunction. Cancer Discovery 10(4):552-567. April 2020. PMID: 32001516.

Frey NV, Shaw PA, Hexner EO, Pequignot E, Gill S, Luger SM, Mangan JK, Loren AW, Perl AE, Maude SL, Grupp SA, Shah NN, Gilmore J, Lacey SF, Melenhorst JJ, Levine BL, June CH, Porter DL. 2020. Optimizing Chimeric Antigen Receptor T-Cell Therapy for Adults With Acute Lymphoblastic Leukemia. J. Clin. Oncol. 38(5): 415-422. Feb 2020. PMID: 31815579.

Kadauke, S, RM Myers, Y Li, R Aplenc, D Baniewicz, DM Barrett, AB Leahy, C Callahan, JG Dolan, JC Fitzgerald, W Gladney, SF Lacey, H Liu, SL Maude, R McGuire, LS Motley, DT Teachey, G Wertheim, L Wray, AM DiNofia, SA Grupp. 2020. Risk-Adapted Preemptive Tocilizumab to Prevent Severe Cytokine Release Syndrome after CTL019 for Pediatric B-Cell Acute Lymphoblastic Leukemia: A Prospective Clinical Trial. J Clin Oncol, in press.

Maus, MV, S Alexander, MR Bishop, JN Brudno, C Callahan, ML Davila, C Diamonte, J Dietrich, JC Fitzgerald, MJ Frigault, TJ Fry, JL Holter-Chakrabarty, KV Komanduri, DW Lee, FL Locke, SL Maude, PL McCarthy, E Mead, SS Neelapu, TG Neilan, BD Santomasso, EJ Shpall, DT Teachey, CJ Turtle, T Whitehead, SA Grupp. 2020. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events. J Immunotherapy Cancer, in press.

2019

Park JR, Kreissman SG, London WB, Naranjo A, Cohn SL, Hogarty MD, Tenney SC, Haas-Kogan D, Shaw PJ, Kraveka JM, Roberts SS, Geiger JD, Doski JJ, Voss SD, Maris JM, Grupp SA, Diller L. 2019. Effect of tandem autologous stem cell transplant vs single transplant on event-free survival in patients with high-risk neuroblastoma: A randomized clinical trial. JAMA 322 (8): 746-755. August 27, 2019. PMID: 31454045. PMCID: PMC6714031.

Laetsch TW, Myers GD, Baruchel A, Dietz AC, Pulsipher MA, Bittencourt H, Buechner J, De Moerloose B, Davis KL, Nemecek E, Driscoll T, Mechinaud F, Boissel N, Rives S, Bader P, Peters C, Sabnis HS, Grupp SA, Yanik GA, Hiramatsu H, Stefanski HE, Rasouliyan L, Yi L, Shah S, Zhang J, Harris AC. 2019. Patient-reported quality of life after tisagenlecleucel infusion in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: a global, single-arm, phase 2 trial. Lancet Oncol. 20 (12): 1710-1718. December 2019. PMID: 31606419.

2018

Maude, SL, TW Laetsch, J Buechner, S Rives, M Boyer, H Bittencourt, P Bader, MR Verneris, HE Stefanski, GD Myers, M Qayed, B De Moerloose, H Hiramatsu, K Schlis, KL Davis, PL Martin, ER Nemecek, GA Yanik, C Peters, A Baruchel, N Boissel, F Mechinaud, A Balduzzi, J Krueger, CH June, BL Levine, P Wood, T Taran, M Leung, KT Mueller, Y Zhang, K Sen, D Lebwohl, MA Pulsipher, and SA Grupp. 2018. Tisagenlecleucel in Children and Young Adults with B Lymphoblastic Leukemia. New England Journal of Medicine. 378(5):439-448. PMID: 29385370.

Teachey DT, Bishop MR, Maloney DG, Grupp SA. 2018. Toxicity management after chimeric antigen receptor T cell therapy: one size does not fit 'ALL'. Nature Reviews Clinical Oncology. April. 15(4):218. PMID: 29434335.

D'Angelo SP, Melchiori L, Merchant MS, Bernstein DB, Glod J, Kaplan RN, Grupp SA, Tap WD, Chagin K, Binder GK, Basu S, Lowther DE, Wang R, Bath N, Tipping A, Betts G, Ramachandran I, Navenot JM, Zhang H, Wells DK, Van Winkle E, Kari G, Trivedi T, Holdich T, Pandite LN, Amado R, Mackall CL. 2018. Antitumor Activity Associated with Prolonged Persistence of Adoptively Transferred NY-ESO-1c259T cells in Synovial Sarcoma. Cancer Discovery 8(8):944-957. PMID: 29891538.

Ruella, M,  J Xu, DM Barrett, JA Fraietta, TJ Reich, DE Ambrose, M Klichinsky, O Shestova, PR Patel, I Kulikovskaya, F Nazimuddin, VG Bhoj, EJ Orlando, TJ Fry, H Bitter, SL Maude, BL Levine, CL Nobles, FD Bushman, RM Young, J Scholler, SI Gill, CH June, SA Grupp, SF Lacey and JJ Melenhorst. October 2018. Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell. **Nature Medicine 24(10): 1499-1503. PMID 30275568.

*Orlando EJ, Han X, Tribouley C, Wood PA, Leary RJ, Riester M, Levine JE, Qayed M, Grupp SA, Boyer M, De Moerloose B, Nemecek ER, Bittencourt H, Hiramatsu H, Buechner J, Davies SM, Verneris MR, Nguyen K, Brogdon JL, Bitter H, Morrissey M, Pierog P, Pantano S, Engelman JA, Winckler W. October 2018. Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia.
**Nature Medicine 24(10): 1504-1506. PMID 30275569.
**same issue

Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. 2018. ASBMT Consensus Grading for Cytokine Release Syndrome and Neurological Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant 25(4): 625-638. PMID 30592986.

2017

Bagatell R, Grupp SA. Refining megatherapy, improving outcome in neuroblastoma. Lancet Oncol. 2017 Apr;18(4):423-424. PMID: 28259607.

Bride, KL, T Vincent, K Smith-Whitley, MP Lambert, JJ. Bleesing, AE Seif, CS Manno, J Casper, SA Grupp, and DT Teachey. 2016. Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial. Blood. 127:17-28. PMID: 26504182, PMCID: PMC4705607.
*Blood Plenary Paper

Singh, N, J Perazzelli, SA Grupp, DM Barrett. 2016. Early memory phenotypes drive T cell proliferation in patients with pediatric malignancies. Sci. Transl. Med. 8, 320ra3. PMID: 26738796.

Teachey, DT, SF Lacey, PA Shaw, JJ Melenhorst, SL Maude, NV Frey, E Pequignot, VE Gonzalez, F Chen, J Finklestein, DM Barrett, SL Weiss, JC Fitzgerald, RA Berg, R Aplenc, C Callahan, SR Rheingold, Z Zheng, S Rose-John, JC White, F Nazimuddin, G Wertheim, BL Levine, CH June, DL Porter, and SA Grupp. 2016. Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T cell Therapy for Acute Lymphoblastic Leukemia. Cancer Discovery 6(6):664-79. PMID: 27076371. PMCID: PMC5448406.

2016

*Ruella, M, DM *Barrett, SS Kenderian, O Shestova, TJ Hofmann, J Perazzelli, M Klichinsky, V Aikawa, F Nazimuddin, M Kozlowski, J Scholler, SF Lacey, JJ Melenhorst, JJD Morrissette, DA Christian, CA Hunter, M Kalos, DL Porter, CH June, SA *Grupp, and S *Gill. 2016. A Novel Strategy for Preventing Antigen-Loss Relapses after CD19-directed Immunotherapies. J. Clinical Investigation. PMID: 27571406.
*equal contribution

Ruella M, Barrett DM, Kenderian SS, Shestova O, Hofmann TJ, Perazzelli J, Klichinsky M, Aikawa V, Nazimuddin F, Kozlowski M, Scholler J, Lacey SF, Melenhorst JJ, Morrissette JJ, Christian DA, Hunter CA, Kalos M, Porter DL, June CH, Grupp SA, Gill S. Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. J Clin Invest. 2016 Oct 3;126(10):3814-3826. PMID: 27571406; PMCID: PMC5096828.

Porter, DL, WT Hwang, NV Frey, SF Lacey, PA Shaw, AW Loren, A Bagg, KT Marcucci, A Shen, V Gonzalez, D Ambrose, SA Grupp, A Chew, Z Zheng, MC Milone, BL Levine, JJ Melenhorst, CH June. 2015. Chimeric Antigen Receptor T Cells Persist and Induce Sustained Remissions in Relapsed Refractory Chronic Lymphocytic Leukemia. Science Translational Medicine. 7:303ra139. PMID: 26333935.

Singh N, Kulikovskaya I, Barrett DM, Binder-Scholl G, Jakobsen B, Martinez D, Pawel B, June CH, Kalos MD, Grupp SA. 2015. T cells targeting NY-ESO-1 demonstrate efficacy against disseminated neuroblastoma. Oncoimmunology. 5(1):e1040216. PMID: 26942053 PMCID: PMC4760344.

2015

Sotillo, E, DM Barrett, KL Black, A Bagashev, D Oldridge, G Wu, R Sussman, C Lanauze, M Ruella, MR Gazzara, NM Martinez, CT Harrington, EY Chung, J Perazzelli, TJ Hofmann, SL Maude, P Raman, A Barrera, S Gill, SF Lacey, JJ Melenhorst, D Allman, E Jacoby, T Fry, C Mackall, Y Barash, KW Lynch, JM Maris, SA Grupp, and A Thomas-Tikhonenko. 2015. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discovery 5(12):1282-95. PMID: 26516065, PMCID: PMC4670800.

2014

Pulsipher, MA, B Langholz, DA Wall, KR Schultz, N Bunin, WL Carroll, E Raetz, S Gardner, JM Gastier-Foser, D Howrie, RK Goyal, JG Douglas, M Borowitz, Y Barnes, DT Teachey, C Taylor, SA Grupp. 2014. The addition of sirolimus to tacrolimus/methotrexate GVHD prophylaxis in children with ALL: A phase 3 Children’s Oncology Group/Pediatric Blood and Marrow Transplant Consortium trial. Blood 123(13): 2017-2025. PMID: 24497539; PMCID: 3968388.

Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter DL, Grupp SA. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014 Oct 16;371(16):1507-17. PMID: 25317870; PMCID: PMC4267531.

2013

Grupp, SA, M Kalos, D Barrett, R Aplenc, DL Porter, SR Rheingold, DT Teachey, BL Levine, and CH June. 2013. Induction of complete remissions of ALL by chimeric antigen receptor-expressing T cells. New England Journal of Medicine. 368(16):1509-18. PMID: 23527958;  PMCID: 4058440; NIHMS: 474709.

Kreissman, SG, RC Seeger, KK Matthay, WB London, R Sposto, SA Grupp, DA Haas-Kogan, MP LaQuaglia, AL Yu, L Diller, A Buxton, JR Park, SL Cohn, JM Maris, CP Reynolds, and JG Villablanca. 2013. Prospective, Randomized Trial of Purged versus Non-Purged Peripheral Blood Stem Cell Transplant for High Risk Neuroblastoma. Lancet Oncology, 14(10):999-1008.  PMID: 23890779 ; PMCID: 3963485; NIHMS: 540046.

Teachey, DT, SR Rheingold, SL Maude, G Zugmaier, DM Barrett, AE Seif, KE Nichols, EK Suppa, M Kalos, RA Berg, JC Fitzgerald, R Aplenc, L Gore, and SA Grupp. 2013. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood. 121(26):5154-5157. PMID: 23678006. NIHMS: 607684.  PMCID: 4123427.