Cliona Rooney, PhD

Professor
Department of Pediatrics
Section of Hematology-Oncology,
Baylor College of Medicine









Contact Information:
cmrooney@texaschildrenshospital.org
832-824-4693

Education:
B.Sc., Genetics, University of East Anglia, England 
Ph.D., Immunology, University of Cambridge, England 

Research Interests:
The research interests of my laboratory are in the immunology and pathogenesis of Epstein-Barr virus, and in immunotherapy for virus-associated malignancies and diseases. In protocols developed with Dr Helen Heslop, over 90 patients have received EBV specific cytotoxic and helper T lymphocytes (CTLs and THLs). These have prevented EBV-associated lymphoma in BMT recipients and cured patients with active disease. They have also produce clinical benefits in patients with chronic active EBV infections and EBV-positive Hodgkin disease. These studies are being expanded to include patients with nasopharyngeal carcinoma and those at risk for post-transplant lymphoproliferative disease after solid organ transplantation. Dr Rooney has developed means to activate and expand single antigen-specific CTL using dendritic cells as antigen-presenting cells. This development allows extension of cell therapy with polyclonal CTL/THL to other infectious diseases and cancers. Most cancers that arise in immunocompetent individuals have mechanisms to evade the immune response, and immunogenic tumors, including Hodgkin tumor cells, survive because they have means to inactive CTL. We have developed methods to render CTL genetically-resistant so some of these immune evasion strategies and we are using animal models to test their safety and efficacy in vivo, before proceeding to clinical trials.

Selected Publications:

Heslop HE, Brenner MK, Rooney CM. Donor T cells to treat EBV-associated lymphoma. N Engl J Med. 1994 Sep 8; 331(10):679-80.

Rooney CM, Smith CA, Ng CYC, Loftin SK, Li C, Krance RA, Brenner MK, Heslop HE. Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr virus-related lymphoproliferation. Lancet. 1995 Jan 7;345(8941):9-13.

Rooney CM, Loftin SK, Holladay MS, Brenner MK, Heslop HE. Early identification of Epstein-Barr virus-associated post-transplantation lymphoproliferative disease. Br J Haematol. 1995 Jan; 89(1):98-103.

Heslop HE, Ng CYC, Li C, Smith, CA Loftin SK Krance RA Brenner MK and Rooney CM. Long term restoration of immunity against Epstein-Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes Nature Medicine. 1996 May; 2(5):551-5.

Roskrow MA, Suzuki N, Gan Y-J, Sixbey JW, Ng CYC, Kimbrough S, Hudson M, Brenner MK, Heslop HE, Rooney CM. EBV-specific cytotoxic T lymphocytes for the treatment of patients with EBV-positive relapsed Hodgkin disease. Blood. 1998 Apr 15; 91(8): 2925-34.

Rooney CM, Smith CA, Ng CYC, Loftin SK, Sixbey JW, Gan YJ, Bowman LC, Krance RA, Brenner MK, Heslop HE. Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients. Blood. 1998 Sep 1;92(5):1549-55.

Gottschalk S, NG C, Perez M, Smith CA, Sample C, Brenner MK, Heslop HE, Rooney CM. An Epstein-Barr virus deletion mutant associated with fatal lymphoproliferative disease unresponsible to therapy with virus-specific CTLs. Blood 2001 Feb 15;97(4): 835-843.

Savoldo B, Cubbage Mi, Durett AG, Goss J. Huls MH, Liu Z, Lopez T, Gee AP, Ling PD, Brenner MK, Heslop HE, Rooney CM. Generation of EBV-specific CD4+ cytotoxic T cells from virus naïve individuals. J Immunol. 2002 Jan 15;168(2):909-18

Rossig C, Bollard CM, Nuchtern JG, Rooney CM, Brenner MK. Epstein –Barr Virus-Specific Human T Lymphocytes Expressing Antitumor Chimeric T Cell Receptors: Potential for Improved Immunotherapy. Blood. 2002 Mar 15;99(6):2009-16.

Bollard CM, Rossig C, Calonge MJ, Huls MH, Wagner HJ, Massague J, Brenner MK, Heslop HE. Adapting a transforming growth factor beta-related tumor protection strategy to enhance antitumor immunity. Blood. 2002 May 1; 99(9): 3179-87

Sili U, Huls MH, Davis AR, Gottschalk S, Brenner MK, Heslop HE and Rooney CM.  Large-Scale Expansion of Dendritic Cell-Primed Polyclonal Human Cytotoxic T-Lymphocyte Lines Using Lymphoblastoid Cell Lines for Adoptive Immunotherapy. J Immunother. 2003 May-Jun;26(3):241-56.

Amrolia PJ, Muccioli-Casadei G, Yvon E, Huls H, Sili U, Wieder ED, Bollard C, Heslop HE, Molldrem JJ, Rooney CM, Brenner MK.  Selective depletion of donor allo-reactive T-cells without loss of anti-viral or anti-leukemic responses.  Blood 2003 Sep 15;102(6):2292-9.

Wagner HJ, Cheng YC, Huls MH, Gee AP, Kuehnle I, Krance RA, Brenner MK, Rooney CM, Heslop HE.  Prompt versus Pre-emptive Intervention for EBV-Lymphoproliferative Disease.  Blood. 2004 May 15;103(10):3979-81

Voo KS, Fu T, Wang HY, Tellam J, Heslop HE, Brenner MK, Rooney CM, Wang RF.  Evidence for the Presentation of Major Histocompatibilty Complex Class I-restricted Epstein-Barr Virus Nuclear Antigen 1 Peptides to CD8+ T Lymphocytes.  J Exp Med  Feb 2004 ;199:459-470.

Wagner H-J, Bollard CM Vigouroux S, Huls MH, Anderson R, Prentice HG,. Brenner MK, Heslop HE, Rooney CM.  A strategy for the treatment of Epstein-Barr virus (EBV)-positive Hodgkin’s disease by targeting interleukin 12 to the tumor environment using tumor antigen specific T cells. Cancer Gene Therapy 2004 Feb;11(2):81-91.

Leen AM, Sili U, Savoldo B, Jewell AM, Piedra PA, Brenner MK, Rooney CM.  Fiber-Modified adenoviruses generate subgroup cross-reactive, adenovirus-specific cytotoxic T lymphocytes for therapeutic applications.  Blood 1 Feb 2004 103(3):1011-1019.

Leen AM, Sili U, Vanin E, Jewell AM, Xie W, Vignali D, Piedra PA, Brenner MK, Rooney CM.  Conserved CTL epitopes on the adenovirus hexon protein expand immunodominant group cross-reactive and group-specific CD8+ T cells.  Blood 2004 Oct 15;104(8):2432-40.

Bollard CM, Aguilar L, Straathof KC, Benedikt G, Huls MH, Rousseau A, Sixbey J, Gresik MV, Carrum G, Hudson M, Dilloo D, Gee A, Brenner MK, Rooney CM, Heslop HE. Cytotoxic T Lymphocyte Therapy for Epstein-Barr Virus Hodgkin’s Disease.  J Exp Medicine 2004 Dec 20; 200(12):1623-1633.

Bollard CM, Straathof KC, Huls MH, Leen A, Lacuesta K, Davis A, Gottschalk S, Brenner MK, Heslop HE, Rooney CM. The generation and characterization of LMP2-specific CTLs for use as adoptive transfer from patients with relapsed EBV-positive Hodgkin disease. J Immunother. 2004 Jul-Aug;27(4):317-27.

Straathof KC, Bollard CM, Popat U, Huls MH, Lopez T, Morriss MC, Gresik MV, Gee AP, Russell HV, Brenner MK, Rooney CM, Heslop HE.  Treatment of Nasopharyngeal Carcinoma with Epstein-Barr Virus-specific T Lymphocytes.  Blood 2005 Mar 1;105(5):1898-904

Straathof KC, Pulè MA, Yotnda P, Dotti G, Vanin EF, Brenner MK, Heslop HE, Spencer DM, Rooney CM. An Inducible Caspase 9 Safety Switch For T Cell Therapy. Blood Jun 2005;105:4247-4254.

Leen AM, Myers GD, Sili U, Huls MH, Weiss H, Leung KS, Carrum G, Krance RA, Chang C-C, Molldrem JJ, Gee AP, Brenner MK, Heslop HE, Rooney CM,  Bollard CM. Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals. Nat Med. 2006 Oct;12(10):1160-1166.

Foster AE, Leen AM, Lee T, Okamura T, Lu A, Vera J, Atkinson R, Dotti G, Rooney CM. Autologous designer antigen presenting cells by gene modification of T lymphocyte blasts with IL-7 and IL-12. J.Immunotherapy 2007 (in press)


 

  

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