Our laboratory's research interests focus on cell therapy with cytotoxic T cells (CTL) for viral and malignant diseases. Led by Catherine Bollard, M.D., we are running clinical trials assessing the safety of adoptively transferred donor-derived virus-specific CTL for the prevention and treatment of viral infection after allogeneic stem cell and cord blood transplant. In addition, we are investigating the utility of this approach using genetically modified virus-specific CTL for the prevention and treatment of viral infection and relapse after transplant. We also are evaluating the efficacy of tumor-specific CTL in patients with relapsed EBV-positive Hodgkin’s disease and non-Hodgkin Lymphoma. Further, we are interested in novel strategies to target the cancer stem cell in lymphoma and to counteract tumor immune evasion mechanisms to enhance the efficacy of adoptive immunotherapy protocols. Alongside Dr. Bollard, we also are exploring the feasibility of expanding T cells targeting non-EBV tumor-associated antigens to treat EBV-negative lymphomas and leukemias as well as HIV.
Dr. Bollard is also the Director of the Program for Emerging Technologies in Immune Cell Therapies.
Laboratory members- Faculty:
Hanley PJ, Melenhorst JJ, Nikiforow S, Scheinberg P, Blaney JW, Demmler-Harrison G, Cruz CR, Lam S, Krance RA, Leung KS, Martinez CA, Liu H, Douek DC, Heslop HE, Rooney CM, Shpall EJ, Barrett AJ, Rodgers JR, Bollard CM. CMV-specific T cells generated from naïve T cells recognize atypical epitopes and may be protective in vivo. Sci Transl Med. 2015 Apr 29;7(285):285ra63.
Lam S, Sung J, Cruz C, Castillo-Caro P, Ngo M, Garrido C, Kuruc J, Archin N, Rooney C, Margolis D, Bollard C. Broadly-specific cytotoxic T cells targeting multiple HIV antigens are expanded from HIV+ patients: implications for immunotherapy. Mol Ther. 2015 Feb;23(2):387-95.
CM Bollard, S Gottschalk, V Torrano, O Diouf, S Ku, Y Hazrat, G Carrum, C Ramos, L Fayad, EJ. Shpall, B Pro, H Liu, MF Wu, D Lee, AM Sheehan, Y Zu, AP Gee, MK Brenner, HE Heslop, CM Rooney. Sustained Complete Responses in Lymphoma Patients Receiving Autologous Cytotoxic T Lymphocytes (CTL) Targeting Epstein-BarrVirus Latent Membrane Proteins. J Clin Oncol. 2014 Mar 10;32(8):798-808
CRY Cruz, KP. Micklethwaite, B Savoldo, CA. Ramos, S Lam, S Ku, O Diouf, E Liu, AJ Barrett, S Ito, EJ Shpall, RA. Krance, RT Kamble, G Carrum, CM. Hosing, AP. Gee, Z Mei, BJ Grilley, HE Heslop, CM Rooney, MK Brenner, CM Bollard, G Dotti. Infusion Of Donor-Derived Cd19-Redirected-Virus-Specific T Cells For B-Cell Malignancies Relapsed After Allogeneic Stem Cell Transplant: A Phase I Study. Blood. 2013 Oct 24;122(17):2965-73. doi: 10.1182/blood-2013-06-506741
G Weber, U Gerdemann, I Caruana, B Savoldo, K Rabin, EJ Shpall, NF Hensel, JJ Melenhorst, AM. Leen, AJ Barrett, CM. Bollard. Generation of multi-leukemia antigen-specific T cells to enhance the graft-versus-leukemia effect after allogeneic stem cell transplant. Leukemia. 2013 Jul;27(7):1538-47. doi: 10.1038/leu.2013.66. Epub 2013 Mar 1.
Cruz CR, Gerdemann U, Leen AM, Shafer JA, Ku S, Tzou B, Horton TM, Sheehan A, Copeland A, Younes A, Rooney CM, Heslop HE, Bollard CM. Improving T-cell therapy for relapsed EBV-negative Hodgkin lymphoma by targeting upregulated MAGE-A4. Clin Cancer Res 2011;17(22):7058-66. doi: 10.1158/1078-0432.CCR-11-1873. Epub 2011 Sep 9.
Hanley PJ, Shaffer DR, Cruz CR, Ku S, Tzou B, Liu H, Demmler-Harrison G, Heslop HE, Rooney CM, Gottschalk S, Bollard CM. Expansion of T cells targeting multiple antigens of cytomegalovirus, Epstein-Barr virus and adenovirus to provide broad antiviral specificity after stem cell transplantation. Cytotherapy 2011;13(8):976-86. doi: 10.3109/14653249.2011.575356. Epub 2011 May 4
Hanley PJ, Cruz CR, Savoldo B, Leen AM, Stanojevic M, Khalil M, Decker W, Molldrem JJ, Liu H, Gee AP, Rooney CM, Heslop HE, Dotti G, Brenner MK, Shpall EJ, Bollard CM. Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopes. Blood 2009;114(9):1958-67. doi: 10.1182/blood-2009-03-213256. Epub 2009 May 14
Leen AM, Myers GD, Sili U, Huls MH, Weiss H, Leung KS, Carrum G, Krance RA, Chang CC, 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;12(10):1160-6. Epub 2006 Sep 24.
Bollard CM, Aguilar L, Straathof KC, Gahn B, 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 Med 2004;200(12):1623-33.