Tumour Immunology

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Lab Head: Associate Professor Rajiv Khanna
Director, Australian Centre for Vaccine Development
Principal Research Fellow, NHMRC

The major goals of the Tumour Immunology Laboratory are to obtain a deeper understanding of the mechanisms by which an immune response to tumors may be generated, augmented and applied to the inhibition of tumor growth. The members of this laboratory share the expectation that such insight will be applicable to the treatment and/or prevention of cancer. The Tumour Immunology laboratory is supported by funding from the National Institutes of Health (US), the National Health and Medical Research Council, the Queensland Cancer Fund and the Leukaemia Foundation.

Some ongoing studies include:

DESIGN OF RECOMBINANT THERAPEUTIC VACCINES TO EBV-ASSOCIATED NASOPHARYNGEAL CARCINOMA AND HODGKIN'S LYMPHOMA
Corey Smith, Maher Gandhi and Rajiv Khanna
Development of vaccine strategies for EBV-associated cancers nasopharyngeal carcinoma (NPC) and Hodgkin’s lymphoma (HL) is a major focus of our laboratory. One such strategy currently under consideration is based on specifically enhancing human immune response to EBV proteins expressed in these cancers. Since both these cancers express identical viral proteins, we anticipate that a common immunotherapeutic protocol may provide curative benefit to cancer bearing patients. We have successfully identified immunogenic determinants from the EBV proteins expressed in NPC and HD and laboratory tests have shown that killer T cells specific for these determinants can efficiently kill these cancer cells. Using these viral determinants we have desigend a therapeutic vaccine (referred to as E1-LMPpoly^TM) which has been extensively tested in preclinical studies and has shown very promising results. It is anticipated that by mid 2007, we will initiate a series of Phase I clinical trials to test the efficacy of this therapeutic vaccine in NPC and HL patients. Various hospitals in Australia (e.g. Peter McCallam Cancer Institute, Princess Alexandra Hospital) and overseas (e.g. University of Hong Kong) will be participating in these multicentre clinical studies. In addition, our group is also negotiating with biotech companies to explore their potential involvement in the future development and commercialisation of this vaccine. Any potential companies interested in licensing E1-LMPpoly^TM technology can contact QIMR Business Development Office or Tumour Immunology Laboratory.

Relevant Publications and Patents or Patent Application for E1-LMPpoly^TM
Thomson, S., KHANNA, R., J. Gardner, S. R. Burrows, B. Coupar, D. J. Moss, and A. Suhrbier, A. Epitopes expressed as a synthetic polyepitope protein are processed and presented to class I to cytotoxic T lymphocytes: implications for vaccine design. Proc. Natl. Acad. Sci. USA (1995) 92: 5845-5849.

KHANNA, R., Busson, P., Burrows, S. R., Raffoux, C., Moss, D. J., Nicholls, J. M. and Cooper, L. Molecular Characterization of Antigen Processing Function in Nasopharyngeal Carcinoma (NPC): Evidence for Efficient Presentation of Epstein-Barr Virus Cytotoxic T Cell Epitopes by NPC Cells. Cancer Res. (1998) 58:310-314.

KHANNA, R., Burrows, S. R., Nicholls J. M. and Poulsen, L. M. Idenfication of Cytotoxic T cell Epitopes within Epstein-Barr Virus (EBV) Oncogene Latent Membrane Protein 1 (LMP1): Evidence for HLA A2 Supertype-Restricted Immune Recognition of EBV-Infected Cells by LMP1-Specific Cytotoxic T Lymphocytes. Europ. J. Immunol. (1998) 28: 451-458.

Duraiswamy, J., Sherritt, M., Thomson, S., Tellam, J., Cooper, L., Connolly, G., Bharadwaj, M., KHANNA, R. Therapeutic LMP1 polyeptiope vaccine for Hodgkin's Disease and Nasopharyngeal Carcinoma. Blood (2003) 101: 3150-3156.

Duraiswamy, J., Burrows, J. M., Bharadwaj, M., Burrows, S. R., Cooper, L., Pimtanothai, N. and KHANNA, R. Ex Vivo Analysis Reveals C-terminal Activator Region 1 and Transmembrane Domain of EBV-Encoded Oncogene LMP1 are Frequent Targets for Virus-Specific T Cell Responses. J. Virol. (2003) 77: 7401-7410.

Duraiswamy, J., Bharadwaj, M., Tellam, J., Connolly, G., Cooper, L., Moss, D. J., Thomson, S., Yotnda, P., and KHANNA, R. Induction of therapeutic T cell responses to subdominant tumour-associated viral oncogene following immunization with replication-incompetent polyepitope adenovirus vaccine. Cancer Research (2004) 64:1483-1489.

KHANNA, R. Moss, D. and Gandhi, M. Application of emerging therapeutic strategies for EBV-associated malignancies. Nature Clinical Practice-Oncology. (2005) 2, 138-149.

Gandhi, M. K., Lambley, E. Burrows, J., Dua, U., Elliott, S., Shaw, P., Miles, H. M., Wolf, M., Clarke, K., Underhill, C., Mills, T., Mollee, P., Gill, D., Marlton, P., Seymour, J.F., KHANNA, R., Plasma Epstein-Barr virus DNA is a biomarker for EBV-positive Hodgkin lymphoma. Clin. Cancer Res. (2006)12: 460-464.

Gandhi, M.K., Lambley, E., Duraiswamy, J., Dua, U., Smith, C., Elliott, S., Gill, D., Marlton, P., Seymour, J., and KHANNA, R. Expression of LAG-3 by tumor-infiltrating lymphocytes is co-incident with the suppression of latent membrane antigen-specific CD8+ T-cell function in Hodgkin lymphoma patient. Blood (2006) 108(7):2280-2289.

Smith, C., Cooper, L., Burgess, M., Rist, M., Webb, N., Lambley, E., Tellam, J., Marlton, P., Seymour J.F., Gandhi, M., and KHANNA, R. Functional reversion of antigen-specific CD8+ T cells from patients with Hodgkin lymphoma following in vitro stimulation with recombinant polyepitope. J. Immunol. (2006) 177(7):4897-906.

Gandhi, M.K., Moll1, G., Dua, U., Lambley, E., Ramuz, O., Smith, C., Gill, D., Marlton, P. Seymour, J. & KHANNA, R. Galectin-1 mediated suppression of EBV-specific T-cell immunity in classical Hodgkin's Lymphoma. Blood (2007) 110: 1326-1329.

Smith, S., Martinez, M., Cooper, L., Rist, M., Zhong, J. and KHANNA, R. Generating functional CD8+ T-cell memory response under transient CD4+ T-cell deficiency: implications for vaccination of immunocompromised individuals. Europ. J. Immunol. (2008) In Press (July issue)

International Patent on Polyepitope Technology (Patent number WO9603144)
International Patent on EBV cytotoxic T cell epitopes (Patent number WO974544)
International Patent on cytotoxic T cell from EBV oncogene LMP1 (Patent number WO9902550)
International Patent Application on LMP-based polyepitope (Patent number WO 2004/041849 A1)

DEVELOPING A PROPHYLACTIC VACCINE FOR HUMAN CYTOMEGALOVIRUS
Jie Zhong, Michael Rist, Tania Crough, and Rajiv Khanna
Human cytomegalovirus (HCMV) is the most significant microbial cause of birth defects, including brain damage and deafness, in developed nations. There is a compelling argument that a reduction in HCMV load would provide significant benefit in improving human health and reducing health care costs. Vaccination is the most practical way to achieve such a reduction in HCMV load. There are two important clinical settings where vaccination will have a significant impact on health outcome. The first is the prevention of the sequelae of congenital HCMV infection. A prophylactic vaccine to prevent congenital HCMV infection would make a major public good and economic contribution by reducing the incidence of birth defects. The second setting is the prevention of HCMV-related complications in organ transplantation. HCMV is a major pathogen in both solid organ and bone marrow transplant recipients. We have identified a large number of cytotoxic T cell epitopes from a variety of HCMV antigens. A subset of epitopes from this group has been nominated for inclusion in a HCMV vaccine on the basis of human immune responsiveness and population coverage. These epitopes form an important component of a prophylactic vaccine for HCMV. Using the QIMR polyepitope technology, a model prophylactic vaccine has been developed which is currently undergoing preclinical testing. Preliminary studies indicate that each of the components of this vaccine is efficiently processed by human cells for display to the immune system and that strong T cell responses are induced when HLA class I transgenic mice are immunised with this vaccine. The HCMV program has also been successful in establishing collaborative links with several biotechnology companies to develop HCMV diagnostic applications. Any potential companies interested in licensing HCMV vaccine technology can contact QIMR Business Development Office or Tumour Immunology Laboratory.

Relevant Publications and International Patent Application for CMV vaccine
Elkington, R.E., Walker, S.W., Crough, T., Menzies, M., Tellam, J. Bharadwaj, M. and KHANNA, R. Ex Vivo Profiling of CD8+ T Cell responses to human cytomegalovirus reveals broad and multispecific reactivities in healthy virus carriers. J. Virol. (2003) 77(9):5226-40.

Burrows, S. R. Elkington, R. A., Miles, J. J., Green, K. J., Walker, S., Haryana, S. M., Moss, D. J., Dunkley, H., Burrows, J. M. and KHANNA, R. Promiscuous CTL recognition of viral epitopes on multiple human leukocyte antigens: Biological validation of the proposed HLA A24 supertype. J. Immunol. (2003) 171:1407-1412.

Elkington, R., Shoukry, N.H., Walker, S., Crough T., Fazou, C., Kaur, A., Walker, C.M. and KHANNA, R. Cross-reactive recognition of human and primate cytomegalovirus sequences by human CD4 cytotoxic T lymphocytes specific for glycoprotein B and H. Europ. J. Immunol. (2004) 34: 3216-3226.

Gandhi, M. and KHANNA, R., Human Cytomegalovirus: Clinical aspects, immune regulation, and emerging treatments. The Lancet Infect. Dis. (2004) 4: 725-738.

Elkington, R. and KHANNA, R., Cross-recognition of human alloantigen by cytomeglaovirus glycoprotein-specific CD4+ cytotoxic T lymphocytes: Implications for graft-versus-host diseases. Blood (2005) 105: 1362-1364.

Crough, T., Burrows, J. M., Fazou, C., Walker, S., Davenport, M.. P. and KHANNA R. Contemporaneous fluctuations in T-cell responses to persistent herpes virus infections. Europ. J. Immunol. (2005) 35:139-145.

Rist, M., Cooper, L., Elkington, R., Walker, S., Fazou C., Tellam, J., Crough, T., and KHANNA, R.. Ex vivo expansion of human cytomegalovirus- specific cytotoxic T Cells by recombinant polyepitope: Implications for HCMV immunotherapy. Europ. J. Immunol. (2005) 35: 996-1007.

KHANNA, R. and Diamond D.J. Human cytomegalovirus vaccine: Time to look for alternative options. Trends Mol. Medicine (2006) 12: 26-33.

Walker, S., Fazou, C., Crough, T., Holdsworth, R., Kiely, P., Veale, M., Bell, S., Gailbraith, A., McNeil, K., Jones, S. and KHANNA, R. Ex Vivo Monitoring of human cytomegalovirus-specific CD8+ T-cell responses using QuantiFERON®-CMV. Transplant Infect. Dis. (2007) 9:165-170. Click here for PDF version

Crough, T, Fazou, C., Weiss, J., Campbell, S., Davenport, M., Bell. S., Galbraith, A., McNeil, K., & KHANNA, R. Symptomatic and asymptomatic viral recrudescence in solid organ transplant recipients and its relationship with antigen-specific CD8+ T-cell response. J. Virol. (2007)81: 11538-11542.

Zhong, J. and KHANNA, R. Vaccine strategies against human cytomegalovirus infection. Expert Rev. Anti-infective Therapy (2007) 5(3):449-459.

Wynn, K.K., Marland, Z., Cooper, L., Silins, S.L., Gras, S., Archbold, J., Tynan, F. E., Miles, J. J., McCluskey, J., Burrows, S. R., Rossjohn, J. & KHANNA, R. Impact of clonal competition for peptide-MHC complexes on the CD8+ T-cell répertoire sélection in a persistent viral infection. Blood (2008) 111: 4283-4292.

International Patent Application on novel HCMV T cell epitopes (Patent application number: AU2002312654)
International Patent Application on HCMV vaccine formulation (Patent application number: AU20040906783)

TARGETING UBIQUITOUSLY EXPRESSED EBV CANCER-ASSOCIATED ANTIGEN EBNA1 FOR IMMUNOTHERAPY
Judy Tellam and Rajiv Khanna
EBV is uniquely associated with a broad range of human malignancies. In spite of their diverse cellular origin, most of these malignancies share common features, including the expression of very limited array of EBV latent proteins, which can be potentially exploited for immune based therapies. EBV-encoded nuclear antigen 1 (EBNA1) is ubiquitously expressed in all EBV-associated cancers and thought to escape killer T cell recognition through either self-inhibition of synthesis or by blockade of proteasomal degradation by an internal glycine-alanine repeat domain (GAr). Our laboratroy has been interested in exploring strategies by which EBNA1 can be targeted for immune recognition and thus provide a single therapeutic strategy for all EBV-associated cancers. Earlier studies from laboratory have shown that cotranslational ubiquitination combined with N-end rule targeting can dramatically enhances the intracellular degradation of EBNA1 and remarkably, leads to induction of a very strong killer T cell response to this protein. More recently, we have shown that EBNA1 displays varied cell type dependent stability; however, these different degradation rates do not correspond to the level of killer T cell recognition. In spite of the highly stable expression of EBNA1 in B cells, CTL epitopes derived from this protein are efficiently processed and presented to killer T cells. Furthermore, we showed that EBV-infected B cells can readily activate EBNA1-specific killer T cell responses from healthy virus carriers. Functional assays revealed that endogenous processing of EBNA1 in virus-infected cells is dependent on the newly synthesized protein rather than the long-lived stable EBNA1. We are currently exploring novel stratagies to increase EBNA1 translation rates by targeting EBNA1's self-inhibiting sequence which may lead to increased killer T cell presentation and thus improve the efficacy of anti-EBV T cell therapy.

Relevant Publications for EBNA1 studies
Tellam, J, Sherrit, M., Thomson, S., Tellam, R., Moss, D.J. Burrows, S.R., Wiertz, E and KHANNA, R. Targeting of EBNA1 for Rapid Intracellular Degradation Overrides the Inhibitory Effects of the Gly-Ala Repeat Domain and Restores CD8+ T Cell Recognition. J. Biol. Chem. (2001) 276: 33353-33360.

KHANNA, R. and Burrows, S. R. Role of cytotoxic T lymphocytes in the control of EBV-associated diseases. Annual Reviews of Microbiology (2000) 54:19-48. (IF:12.105)

KHANNA, R., Tellam, J., Duraiswamy, D. and Copper, L. Immunotherapeutic strategies for EBV-associated malignancies. Trends In Mol. Medicine (2001) 7:270-276.

Tellam, J., Connolly, G., Green, K., Miles, J., Moss, D. J., Burrows, S. R. and KHANNA, R., Endogenous processing of CD8+ T cells epitopes from Epstein-Barr virus encoded nuclear antigen 1. J. Exp. Med. (2004) 199(10):1421-1431.

Tellam, J., Rist, M., Conolly, G., Webb, N., Fazou, C. and Wang, F., and KHANNA, R., Translation efficiency of EBNA1 encoded by lymphocryptoviruses influences endogenous presentation of CD8+ T cell epitopes. Europ. J. Immunol (2007) 37(2):328-337.

Tellam, J., Fogg, M. H., Rist, M., Conolly, G., Tscharke, D., Webb, N., Heslop, L, Wang, F., and KHANNA R. Influence of translation efficiency of homologous viral proteins on the endogenous presentation of CD8+ T cell epitopes. J. Exp. Med. (2007) 204:525-532.

Tellam, J., Smith, C., Rist, M., Webb, N., Cooper, L., Vuocolo, T., Connolly, G., Tscharke, D., Devoy, M. and KHANNA, R. Regulation of protein translation through mRNA structure influences MHC Class I loading and T cell recognition. Proc. Natl Acad. Sci. USA (2008) In Press

Staff

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Student Projects

The Tumour Immunology Laboratory has a number of projects available for students. For more details, please contact A/Prof Rajiv Khanna: rajivK@qimr.edu.au

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Other Select Publications

Reprints for these publications are available by email from Assoc Prof Rajiv Khanna

KHANNA, R., Burrows, S.R. Kurilla, M.G., Jacob, C.A., Misko, I.S., Sculley, T.B., Kieff, E. and Moss, D.J. Localisation of Epstein-Barr virus CTL epitopes using recombinant vaccinia: implications for vaccine development. J. Exp. Med. (1992) 176 169-176.

KHANNA, R. Burrows, S.R., Suhrbier, A., Jacob, C.A., Griffin, H., Misko, I.S., Sculley, T.B., Rowe, M., Rickinson, A.B. and Moss, D.J. Epstein-Barr virus peptide epitope sen sitisation restores human cytotoxic T cell recognition of Burkitt's lymphoma cells: Evidence for a critical role for ICAM2. J. Immunol. (1993) 150: 5154-5162.

Burrows, S.R., KHANNA, R., Burrows, J.M. and Moss, D.J. An alloresponse in humans is dominated by cytotoxic T lymphocytes (CTL) cross-reactive with a single Epstein-Barr virus CTL epitope: Implications for graft-verses-host disease. J. Exp. Med. (1994) 179: 1155-1161.

KHANNA, R., S. R. Burrows, V. Argaet & D. J. Moss. Endoplasmic reticulum signal sequence facilitated transport of peptide epitopes restores immunogenicity of an antigen processing defective tumor cell line. Inter. Immunol. (1994) 6: 639-645.

KHANNA, R., Rowe, M., Jacob, C.A., Argaet, V., Kelly, A., Powis, S., Burrows, S.R., Trowsdale, J., Moss, D.J., and Rickinson, A.B. Restoration of endogenous antigen processing in Burkitt's Lymphoma cells by Epstein-Barr virus latent membrane protein-1: Coordinate upregulation of peptide transporters and HLA-class I antigen expression. Europ. J. Immunol. (1995) 25: 1374-1384.

Burrows, S.R., Silinis, S., Moss, D.J., KHANNA, R., Misko, I.S. and Argaet, V.P. T cell receptor repertoire for a viral epitope in humans is diversified by tolerance to a background MHC antigen. J. Exp. Med. (1995) 182:1703-1715.

KHANNA, R., Burrows, S. R., Thomson, S. A., Moss, D. J., Cresswell, P., Poulsen, L. M. and Cooper, L. Class I processing-defective Burkitt's lymphoma cells are efficiently recognized by CD4+ EBV-specific CTL. J. Immunol. (1997) 158:3619-3625.

KHANNA, R., Cooper, L., Moss, D. J., Keinzel, N., Burrows, S. R., Khanna, K. K. Engagement of CD40 antigen on with soluble CD40 ligand upregulates peptide transporter expression and restores endogenous processing function in Burkitt's lymphoma cells. J. Immunol (Cutting Edge) (1997) 159:5782-5785.

Peh, A. C., Burrows, S. R., KHANNA, R., Cresswell, P., Moss, D. J. and McCluskey, J. HLA B27-restricted antigen presentation in the absence of the tapasin reveals polymorphism in generic mechanism of HLA class I-peptide loading. Immunity (1998) 8: 531-542.

KHANNA, R., Sherrit, M. And Burrows, S. R. EBV structural antigens, gp350 and gp85, as targets for ex vivo virus-specific CTLs during acute infectious mononucleosis: Potential use of gp350/gp85 CTL epitopes for vaccine design. J. Immunol. (1999) 162:3063-3069.

Kienzle, N., Sculley, T. B., Greco, S. and KHANNA, R. Silencing virus-specific cytotoxic T cell-mediated immune recognition by differential splicing: A novel role of RNA processing for antigen presentation. J. Immunol. (Cutting Edge) (1999)162: 6963-6966.

KHANNA, R., Bell, S., Sherritt, M., Galbraith, A., Burrows, S. R., Rafter, L., Clarke, B., Slaughter, R., Falk, M. C., Douglas, J., Willams, T., Moss, D. J. Activation and adoptive transfer of Epstein-Barr virus-specific cytotoxic T cells in solid organ transplnat patients with posttransplant lymphoproliferative disease. Proc. Natl. Acad. Sci. (USA) (1999) 96:10391-10396.

Kienzle, N., Buck, M., Silins, S. L., Burrows, S.R., Moss, D.J., Winterhalter, A., Brooks, A. and KHANNA, R. Differential splicing of antigen-encoding RNA reduces endoegnous epitope presentation which regulates the expansion and cytotxicity of T cells. J. Immunol. (2000) 165: 1840-1846.

Bharadwaj, M., Burrows, S. R., Burrows, J. M., Moss, D. J., Catalina, M. and KHANNA, R. Longitudinal dynamics of antigen-specific CD8+ cytotoxic T lymphocytes following primary EBV infection. Blood (2001) 98:2588-2589.

Tellam, J., Connolly, G., Webb, N., Duraiswamy, J. and KHANNA, R. Proteasomal targeting of a viral oncogene abrogates oncogenic phenotype and enhances immunogenicity. Blood (2003) 102: 4535-4540.

KHANNA, R. and Burrows, S. R. Role of cytotoxic T lymphocytes in the control of EBV-associated diseases. Annual Reviews of Microbiology (2000) 54:19-48.

Pai, S. and KHANNA, R. Role of LMP1 protein in the immune control of EBV infection. Seminars in Cancer Biology (2001) 11: 455-460.

Burrows, J.M., Bromham, L., Woolfit, M., Piganeau, G., Tellam, J., Connolly, G., Webb, N., Poulsen, L., Cooper, L., Burrows, S. R., Moss, D. J., Haryana, S.M., Ng, M., Nicholls, J. M., and KHANNA, R. Selection Pressure Driven Evolution of the Epstein-Barr virus Encoded Oncogene, LMP1, in Virus Isolates from South-East Asia. J. Virol. (2004) 78: 7131-7137.

Gandhi, M., Tellam, J. & KHANNA, R., Epstein-Barr virus associated Hodgkin's disease. British J. Haematology (2004) 125(3):267-81.

Pai, S., O'Sullivano, B., Abdul-Jabbaro, I., Pengo, J., Connoly, G., KHANNA, R. and Thomas R. Nasopharyngeal carcinoma-associated EBV-encoded oncogene latent membrane protein 1 potentiates regulatory T cell function. Immunol. Cell Biol. (2007) 85: 370-377(IF: 2.482)

Nehring, A.K., Dua, U., Mollee, P., Gill, D., Grimmett, K., KHANNA, R.., Moss, D., Gandhi, M. K. Epstein-Barr virus T-cell immunity despite rituximab. Br J Haematol. (2007) 136(4):628-32.

Burrows, J.M., Wynn, K., Tynan, F.E., Archbold, J., Miles, J.J., Bell, M.J., Brennan, R.M., Walker, S., Rossjohn, J., KHANNA, R. and Burrows, S.R. HLA Micropolymorphism outside Primary Peptide Anchor Pockets has a Major Impact on Determinant Selection in the CTL Response to CMV. Europ. J. Immunol. (2007) 37(4):946-953

Crompton, L., Khan, N., KHANNA, R., Nayak, L. and Moss, P.A. CD4+ T cells specific for glycoprotein B from cytomegalovirus exhibit extreme conservation of T cell receptor usage between different individuals: Potential implications for Large granular lymphocytosis. Blood (2008) 111: 2053-2061(IF 10.370).

Burrows, J.M., Bell, M.J., Brennan, R., Miles J.J., KHANNA, R. and Burrows, S.R. Preferential binding of unusually long peptides to MHC class I and its influence on the selection of target peptides for T cell recognition. Molecular Immunology (2008) 45: 1818-1824

Moss, D. J., Burrows, S. R. and KHANNA, R. Vaccine Based Approaches: (2005) in Infection, Pathogenesis, Molecular Biology and Control of Epstein-Barr virus Edited by Erle S. Robertson. Publisher Horizon Press pp 253-267.

Morgan, A. J. and KHANNA, R., Epstein-Barr virus: Section VI: Vaccines and Immunotherapy (2007) in Human herpesviruses: Biology, Therapy and Immunoprophylaxis Eds:Ann M. Arvin, G. Campadielli-Fume, B. Roizman, R. Whitley & K. Yamanishi pp.1265-1277

Moss, D. J., Burrows, . R. and KHANNA, R., Immunobiology of Epstein-Barr virus: (2007) in Human herpesviruses: Biology, Therapy and Immunoprophylaxis Eds:Ann M. Arvin, G. Campadielli-Fume, B. Roizman, R. Whitley & K. Yamanishi pp882-892

Smith, C., and KHANNA, R. Polyepitope Vaccines for Human Cancers (2007). In Cancer Vaccines and Tumor Immunity, Ed: Hodge, J., Johnson, B. and Orentas, R. John Wiley and Sons, Inc. Hoboken, NJ. In press.

Smith, C., and KHANNA, R., Immunotherapeutic strategies for nasopharyngeal carcinoma (2007) In Nasopharyngeal Carcinomas Ed: Dr. Pierre Busson. Landes Biosciences, Austin, TX In press

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