Helen E. Heslop, M.D., FRACP, FRCPA
Department Medicine - Hematology-Oncology
- M.B., Ch.B., Otago University Medical School, New Zealand
- M.D., Otago University Medical School, New Zealand
- Fellow, Department of Haematology, Royal Free Hospital, London, England
Helen Heslop's research interest is adoptive immunotherapy with antigen specific cytotoxic T lymphocytes to augment antiviral and antitumor immunity. The research projects in this program test immunotherapy strategies for preventing and treating viral infections and malignancy. A key step in this strategy has been the translation of laboratory findings to Phase I and II clinical trials, as exemplified by studies of Epstein Barr virus-induced lymphoproliferative disease (EBV-LPD), a fatal complication in about 15% of recipients of unrelated or mismatched family member bone marrow transplants in the early 1990s. In collaboration with Dr Cliona Rooney, she developed methods for early diagnosis of this disease and procedures for generating cytotoxic T lymphocytes (CTLs) from bone marrow donors. Ultimately, she and her group undertook clinical trials showing that adoptively transferred CTLs were successful in preventing or eradicating EBV-LPD following bone marrow transplantation.
The success of these studies led to trials of EBV- specific CTLs in other EBV -associated malignancies (Hodgkin's disease and nasopharyngeal cancer) in which the tumor cells are less immunogenic than the ones treated previously. They are also currently evaluating if persistence and expansion of CTLs can be improved by pre-treatment of patients with lymphodepleting antibodies or vaccination with Class I or II peptides. They are also using similar approaches to generate antiviral CTLs specific for CMV and adenovirus for administration to patients post transplant. Other areas of research focus include identification of novel tumor antigens and genetic modification of CTLs to overcome tumor evasion strategies. In collaboration with Dr Brenner's group they are also evaluating if transduction of CTLs with chimeric antigen receptors can allow targeting of CD19+ve, CD30+ve and her2neu+ve malignancies. Dr Heslop holds a Doris Duke Distinguished Clinical Scientist Award.
- Williams LL, Rooney CM, Conley ME, Brenner MK, Krance RA, Heslop HE. Correction of Duncan's syndrome by allogeneic bone marrow transplantation. Lancet 342:587-588, 1993.
- Rooney CM, Loftin SK, Holladay MS, Brenner MK, Krance RA, Heslop HE. Early identification of Epstein-Barr virus-associated post-transplantation lymphoproliferative disease. Br J Haematol 89:98-103, 1995.
- Rooney CM, Smith CA, Ng C, 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 345:9-13, 1995.
- Heslop HE, Benaim E, Brenner MK, Krance RA, Stricklin LM, Rochester RA, Billings R. Response of steroid-resistant graft-versus-host disease to lymphoblast antibody CBL1. Lancet 346:805-806, 1995.
- Heslop HE, Ng CYC, Li C, Smith CA, Loftin SK, Krance RA, Brenner MK, Rooney CM. Long term restoration of immunity against Epstein-Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes. Nature Medicine 2:551-555, 1996.
- Hongeng S, Krance RA, Bowman LC, Srivastava DK, Cunningham JM, Horwitz E, Brenner MK, Heslop HE. Identical outcome of matched sibling and matched unrelated donor bone marrow transplantation in pediatric leukemia patients. Lancet 350:767-770, 1997.
- Rooney CM, Smith AA, Ng CYC, Loftin SK, Sixbey JW, Gan Y, 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 92:1549-1555, 1998.
- Heslop HE. Haemopoietic stem cell transplantation from unrelated donors. Br J Haematol 105:2-6, 1999
- Kuehnle I, Huls MH, Liu Z, Semelmann M, Krance RA, Brenner MK, Rooney CM, Heslop HE. CD20 Monoclonal Antibody (Rituximab) for Therapy of EBV Lymphoma after Hemopoietic Stem Cell Transplant Blood 95:1502-1505, 2000.
- 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 unresponsive to therapy with virus-specific CTLs.. Blood, 97:835-43, 2001.
- Bollard CM, Rossig C, Calonge MJ, Huls MH, Wagner HJ, Massague J, Brenner MK, Heslop HE, Rooney CM. Adapting a transforming growth factor beta-related tumor protection strategy to enhance antitumor immunity. Blood. 2002;99:3179-3187.
- Gottschalk S, Heslop HE, Rooney CM Treatment of Epstein-Barr virus associated Malignancies with specific T cells. Adv Cancer Res 84:175-201, 2002.
- Wagner HJ, Rooney CM, Heslop HE Diagnosis and Treatment of Post-transplant Lymphoproliferative Disease after Hematopoietic Stem Cell Transplantation Biol Blood Marrow Trans 8:1-8. 2002.
- Wagner, H. J., Cheng, Y. C., Huls, M. H., Gee, A. P., Kuehnle, I., Krance, R. A., Brenner, M. K., Rooney, C. M., and Heslop, H. E. Prompt versus Pre-emptive Intervention For EBV- Lymphoproliferative Disease. Blood 2004. 103:3979-81
- Gottschalk S, Rooney CM, Heslop HE. Post-Transplant Lymphoproliferative Disorders. Annu Rev Med. 2005 ;56:29-44
- Bollard CM, Aguilar L>, Straathof KC, Gahn B, Huls MH, Rousseau A, Sixbey J, Gresik MV, Carrum G, Hudson M, Dilloo D, Gee AP, >Brenner MK, >Rooney CM, Heslop HE Cytotoxic T Lymphocyte Therapy for EBV-Positive Hodgkin's Disease J Exp Med. 2004 Dec 20;200(12):1623-33.
- 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. 105:1898-904.
- Savoldo,B., Goss,J.A., Hammer,M., Zhang,L., Lopez T, Gee AP, Lin Y-F, Quiros-Tejeira RE, Reinke P, Schubert S, Gottschalk,S., Finegold,M., Brenner M.K., Rooney,C.M., Heslop,H.E. Autologous Epstein Barr Virus-Specific Cytotoxic T Lymphocyte (CTL) Infusions For Solid Organ Transplant Recipients. Blood 2006;108:2942-2949.
- Leen A>, Myers GD, Sili U, Huls MH, Leung K, Carrum G, Krance RA, Weiss H, 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 patients. Nat Med. 2006;12:1160-1166