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Todd Schell

TitleAssociate Professor
InstitutionCollege of Medicine
DepartmentMicrobiology and Immunology
Address500 University Drive Hershey PA 17033
Mailbox: H107
Phone7175315577

 Overview 
 overview
PREFERRED TITLE/ROLE:

Associate Professor of Microbiology and Immunology

GRADUATE PROGRAM AFFILIATIONS:

Microbiology and Immunology, MD/PhD Degree Program, Cell and Molecular Biology, Immunology and Infectious Diseases, Biomedical Sciences (Virology and Immunology Option)

EDUCATION:

Ph.D., West Virginia University, 1995
Postdoctoral Training, Penn State College of Medicine, 1995-1999

NARRATIVE:

My research interests focus on the role of the cellular immune response in the control of cancer. CD8+, or cytotoxic, T lymphocytes (CTL) have been implicated as critical components of the immune response to tumors with the ability to directly lyse tumor cells as well as secrete cytokines which suppress tumor growth. Approaches that lead to successful T cell-mediated control of tumor progression, however, are inhibited by the development of T lymphocyte tolerance toward potential tumor antigens that also represent "self" antigens. Thus, my interests are in developing strategies to recruit tumor-specific CD8+ T cells under conditions of self tolerance for the immunotherapy of cancer.

The model system we use to study the CD8+ T cell response to cancer is the Simian virus 40 oncoprotein large T antigen. T antigen serves as both a transforming protein, inducing tumor progression when expressed as a transgene in mice, and contains multiple CD8+ T cell-recognized epitopes designated epitopes I, II/III, IV and V. This model provides a platform to assess approaches that target immunity against a well characterized "self" antigen in the context of progressing cancer. We are interested in defining which epitopes are important for control of tumors that arise in T antigen transgenic mice. Our recent studies have revealed that: 1) targeting the H2-Kb-restricted epitope IV of T antigen is associated with the control of tumor progression in T antigen transgenic mice, 2) Epitope IV-specific CD8+ T cells can be detected at the tumor site using a fluorescently-labeled tetrameric Kb/epitope IV reagent, 3) These cells have both lytic function and secrete interferon-gamma in response to antigen, and 4) T antigen expression in the peripheral tissues limits the responsiveness of CD8+ T cells specific for each of the T antigen epitopes I, II/III, IV and V, but the timing of tolerance onset varies for each epitope. In particular, the onset of tolerance to epitope IV correlated directly with the appearance of tumors. This suggests that a window of opportunity exists for immunization against tumors and that epitope selection is critical for the immunotherapy of cancer. We are interested, therefore, in determining if CD8+ T cells can be recruited from within this limited T cell repertoire that can effectively mediate control of tumor progression. This research involves a number of approaches aimed at enhancing the surviving CD8+ T cell response to the subdominant epitope V in T antigen transgenic mice for the control of progressing tumors.


 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Cozza EM, Cooper TK, Budgeon LR, Christensen ND, Schell TD. Protection from tumor recurrence following adoptive immunotherapy varies with host conditioning regimen despite initial regression of autochthonous murine brain tumors. Cancer Immunol Immunother. 2015 Mar; 64(3):325-36.
    View in: PubMed
  2. Ward-Kavanagh LK, Zhu J, Cooper TK, Schell TD. Whole-body irradiation increases the magnitude and persistence of adoptively transferred T cells associated with tumor regression in a mouse model of prostate cancer. Cancer Immunol Res. 2014 Aug; 2(8):777-88.
    View in: PubMed
  3. Richie JP, Nichenametla S, Neidig W, Calcagnotto A, Haley JS, Schell TD, Muscat JE. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr. 2015 Mar; 54(2):251-63.
    View in: PubMed
  4. Sagar D, Masih S, Schell T, Jacobson S, Comber JD, Philip R, Wigdahl B, Jain P, Khan ZK. In vivo immunogenicity of Tax(11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine. Vaccine. 2014 May 30; 32(26):3274-84.
    View in: PubMed
  5. Rytelewski M, Meilleur CE, Yekta MA, Szabo PA, Garg N, Schell TD, Jevnikar AM, Sharif S, Singh B, Haeryfar SM. Suppression of immunodominant antitumor and antiviral CD8+ T cell responses by indoleamine 2,3-dioxygenase. PLoS One. 2014; 9(2):e90439.
    View in: PubMed
  6. Goodwin EM, Zhong Q, Abendroth CS, Ward-Kavanagh LK, Schell TD, Cooper TK. Anaplastic renal carcinoma expressing SV40 T antigen in a female TRAMP mouse. Comp Med. 2013 Aug; 63(4):338-41.
    View in: PubMed
  7. Watson AM, Mylin LM, Thompson MM, Schell TD. Modification of a tumor antigen determinant to improve peptide/MHC stability is associated with increased immunogenicity and cross-priming a larger fraction of CD8+ T cells. J Immunol. 2012 Dec 15; 189(12):5549-60.
    View in: PubMed
  8. Clawson GA, Kimchi E, Patrick SD, Xin P, Harouaka R, Zheng S, Berg A, Schell T, Staveley-O'Carroll KF, Neves RI, Mosca PJ, Thiboutot D. Circulating tumor cells in melanoma patients. PLoS One. 2012; 7(7):e41052.
    View in: PubMed
  9. Wilson JJ, Pack CD, Lin E, Frost EL, Albrecht JA, Hadley A, Hofstetter AR, Tevethia SS, Schell TD, Lukacher AE. CD8 T cells recruited early in mouse polyomavirus infection undergo exhaustion. J Immunol. 2012 May 1; 188(9):4340-8.
    View in: PubMed
  10. Avella DM, Li G, Schell TD, Liu D, Zhang SS, Lou X, Berg A, Kimchi ET, Tagaram HR, Yang Q, Shereef S, Garcia LS, Kester M, Isom HC, Rountree CB, Staveley-O'Carroll KF. Regression of established hepatocellular carcinoma is induced by chemoimmunotherapy in an orthotopic murine model. Hepatology. 2012 Jan; 55(1):141-52.
    View in: PubMed
  11. Maleki Vareki S, Harding MJ, Waithman J, Zanker D, Shivji AN, Rytelewski M, Mazzuca DM, Yekta MA, Chen W, Schell TD, Haeryfar SM. Differential regulation of simultaneous antitumor and alloreactive CD8(+) T-cell responses in the same host by rapamycin. Am J Transplant. 2012 Jan; 12(1):233-9.
    View in: PubMed
  12. Campbell C, Zhang R, Haley JS, Liu X, Loughran T, Schell TD, Albert R, Thakar J. Why Do CD8+ T Cells become Indifferent to Tumors: A Dynamic Modeling Approach. Front Physiol. 2011; 2:32.
    View in: PubMed
  13. Fateh S, Schell TD, Gingrich R, Neves RI, Drabick JJ. Unsuccessful high dose IL-2 therapy followed immediately by near continuous low dose temozolomide can result in rapid durable complete and near-complete remissions in metastatic melanoma. Cancer Biol Ther. 2010 Dec 1; 10(11):1091-7.
    View in: PubMed
  14. Drabick JJ, Schell TD. Poking CD40 for cancer therapy, another example of the Goldilocks effect. Cancer Biol Ther. 2010 Nov 15; 10(10):994-6.
    View in: PubMed
  15. Hu J, Schell TD, Peng X, Cladel NM, Balogh KK, Christensen ND. Using HLA-A2.1 Transgenic Rabbit Model to Screen and Characterize New HLA-A2.1 Restricted Epitope DNA Vaccines. J Vaccines Vaccin. 2010 Aug 20; 1(1).
    View in: PubMed
  16. Tatum AM, Watson AM, Schell TD. Direct presentation regulates the magnitude of the CD8+ T cell response to cell-associated antigen through prolonged T cell proliferation. J Immunol. 2010 Sep 1; 185(5):2763-72.
    View in: PubMed
  17. Manuel SL, Schell TD, Acheampong E, Rahman S, Khan ZK, Jain P. Presentation of human T cell leukemia virus type 1 (HTLV-1) Tax protein by dendritic cells: the underlying mechanism of HTLV-1-associated neuroinflammatory disease. J Leukoc Biol. 2009 Nov; 86(5):1205-16.
    View in: PubMed
  18. Ryan CM, Staveley-O'Carroll K, Schell TD. Combined anti-CD40 conditioning and well-timed immunization prolongs CD8+ T cell accumulation and control of established brain tumors. J Immunother. 2008 Nov-Dec; 31(9):906-20.
    View in: PubMed
  19. Tatum AM, Mylin LM, Bender SJ, Fischer MA, Vigliotti BA, Tevethia MJ, Tevethia SS, Schell TD. CD8+ T cells targeting a single immunodominant epitope are sufficient for elimination of established SV40 T antigen-induced brain tumors. J Immunol. 2008 Sep 15; 181(6):4406-17.
    View in: PubMed
  20. de Witte MA, Bendle GM, van den Boom MD, Coccoris M, Schell TD, Tevethia SS, van Tinteren H, Mesman EM, Song JY, Schumacher TN. TCR gene therapy of spontaneous prostate carcinoma requires in vivo T cell activation. J Immunol. 2008 Aug 15; 181(4):2563-71.
    View in: PubMed
  21. Tagaram HR, Watson AM, Lemonnier FA, Staveley-O'Carroll K, Tevethia SS, Schell TD. An SV40 VP1-derived epitope recognized by CD8+ T cells is naturally processed and presented by HLA-A*0201 and cross-reactive with human polyomavirus determinants. Virology. 2008 Jun 20; 376(1):183-90.
    View in: PubMed
  22. Yorty JL, Tevethia SS, Schell TD. Rapid accumulation of adoptively transferred CD8+ T cells at the tumor site is associated with long-term control of SV40 T antigen-induced tumors. Cancer Immunol Immunother. 2008 Jun; 57(6):883-95.
    View in: PubMed
  23. Otahal P, Knowles BB, Tevethia SS, Schell TD. Anti-CD40 conditioning enhances the T(CD8) response to a highly tolerogenic epitope and subsequent immunotherapy of simian virus 40 T antigen-induced pancreatic tumors. J Immunol. 2007 Nov 15; 179(10):6686-95.
    View in: PubMed
  24. Mylin LM, Schell TD, Epler M, Kusuma C, Assis D, Matsko C, Smith A, Allebach A, Tevethia SS. Diversity of escape variant mutations in Simian virus 40 large tumor antigen (SV40 Tag) epitopes selected by cytotoxic T lymphocyte (CTL) clones. Virology. 2007 Jul 20; 364(1):155-68.
    View in: PubMed
  25. Hu J, Peng X, Schell TD, Budgeon LR, Cladel NM, Christensen ND. An HLA-A2.1-transgenic rabbit model to study immunity to papillomavirus infection. J Immunol. 2006 Dec 1; 177(11):8037-45.
    View in: PubMed
  26. Otahal P, Schell TD, Hutchinson SC, Knowles BB, Tevethia SS. Early immunization induces persistent tumor-infiltrating CD8+ T cells against an immunodominant epitope and promotes lifelong control of pancreatic tumor progression in SV40 tumor antigen transgenic mice. J Immunol. 2006 Sep 1; 177(5):3089-99.
    View in: PubMed
  27. Sheil JM, Frankenberry MA, Schell TD, Brundage KM, Barnett JB. Propanil exposure induces delayed but sustained abrogation of cell-mediated immunity through direct interference with cytotoxic T-lymphocyte effectors. Environ Health Perspect. 2006 Jul; 114(7):1059-64.
    View in: PubMed
  28. Ryan CM, Schell TD. Accumulation of CD8+ T cells in advanced-stage tumors and delay of disease progression following secondary immunization against an immunorecessive epitope. J Immunol. 2006 Jul 1; 177(1):255-67.
    View in: PubMed
  29. Otahal P, Hutchinson SC, Mylin LM, Tevethia MJ, Tevethia SS, Schell TD. Inefficient cross-presentation limits the CD8+ T cell response to a subdominant tumor antigen epitope. J Immunol. 2005 Jul 15; 175(2):700-12.
    View in: PubMed
  30. Barton LF, Runnels HA, Schell TD, Cho Y, Gibbons R, Tevethia SS, Deepe GS, Monaco JJ. Immune defects in 28-kDa proteasome activator gamma-deficient mice. J Immunol. 2004 Mar 15; 172(6):3948-54.
    View in: PubMed
  31. Schell TD. In vivo expansion of the residual tumor antigen-specific CD8+ T lymphocytes that survive negative selection in simian virus 40 T-antigen-transgenic mice. J Virol. 2004 Feb; 78(4):1751-62.
    View in: PubMed
  32. Stanic AK, Shashidharamurthy R, Bezbradica JS, Matsuki N, Yoshimura Y, Miyake S, Choi EY, Schell TD, Van Kaer L, Tevethia SS, Roopenian DC, Yamamura T, Joyce S. Another view of T cell antigen recognition: cooperative engagement of glycolipid antigens by Va14Ja18 natural T(iNKT) cell receptor [corrected]. J Immunol. 2003 Nov 1; 171(9):4539-51.
    View in: PubMed
  33. Staveley-O'Carroll K, Schell TD, Jimenez M, Mylin LM, Tevethia MJ, Schoenberger SP, Tevethia SS. In vivo ligation of CD40 enhances priming against the endogenous tumor antigen and promotes CD8+ T cell effector function in SV40 T antigen transgenic mice. J Immunol. 2003 Jul 15; 171(2):697-707.
    View in: PubMed
  34. Anglen CS, Truckenmiller ME, Schell TD, Bonneau RH. The dual role of CD8+ T lymphocytes in the development of stress-induced herpes simplex encephalitis. J Neuroimmunol. 2003 Jul; 140(1-2):13-27.
    View in: PubMed
  35. Schell TD, Mylin LM, Tevethia SS, Joyce S. The assembly of functional beta(2)-microglobulin-free MHC class I molecules that interact with peptides and CD8(+) T lymphocytes. Int Immunol. 2002 Jul; 14(7):775-82.
    View in: PubMed
  36. Schell TD, Tevethia SS. Control of advanced choroid plexus tumors in SV40 T antigen transgenic mice following priming of donor CD8(+) T lymphocytes by the endogenous tumor antigen. J Immunol. 2001 Dec 15; 167(12):6947-56.
    View in: PubMed
  37. Schell TD, Lippolis JD, Tevethia SS. Cytotoxic T lymphocytes from HLA-A2.1 transgenic mice define a potential human epitope from simian virus 40 large T antigen. Cancer Res. 2001 Feb 1; 61(3):873-9.
    View in: PubMed
  38. Schell TD, Tevethia SS. Cytotoxic T lymphocytes in SV40 infections. Methods Mol Biol. 2001; 165:243-56.
    View in: PubMed
  39. Tevethia S, Beachy T, Schell T, Lippolis J, Newmaster R, Mylin L, Tevethia MJ. Role of CTL host responses and their implication for tumorigenicity testing and the use of tumour cells as vaccine substrate. Dev Biol (Basel). 2001; 106:109-21; discussion 143-60.
    View in: PubMed
  40. Mylin LM, Schell TD, Roberts D, Epler M, Boesteanu A, Collins EJ, Frelinger JA, Joyce S, Tevethia SS. Quantitation of CD8(+) T-lymphocyte responses to multiple epitopes from simian virus 40 (SV40) large T antigen in C57BL/6 mice immunized with SV40, SV40 T-antigen-transformed cells, or vaccinia virus recombinants expressing full-length T antigen or epitope minigenes. J Virol. 2000 Aug; 74(15):6922-34.
    View in: PubMed
  41. Schell TD, Knowles BB, Tevethia SS. Sequential loss of cytotoxic T lymphocyte responses to simian virus 40 large T antigen epitopes in T antigen transgenic mice developing osteosarcomas. Cancer Res. 2000 Jun 1; 60(11):3002-12.
    View in: PubMed
  42. Schell TD, Mylin LM, Georgoff I, Teresky AK, Levine AJ, Tevethia SS. Cytotoxic T-lymphocyte epitope immunodominance in the control of choroid plexus tumors in simian virus 40 large T antigen transgenic mice. J Virol. 1999 Jul; 73(7):5981-93.
    View in: PubMed
  43. Fu TM, Mylin LM, Schell TD, Bacik I, Russ G, Yewdell JW, Bennink JR, Tevethia SS. An endoplasmic reticulum-targeting signal sequence enhances the immunogenicity of an immunorecessive simian virus 40 large T antigen cytotoxic T-lymphocyte epitope. J Virol. 1998 Feb; 72(2):1469-81.
    View in: PubMed
  44. Sheil JM, Schell TD, Shepherd SE, Klimo GF, Kioschos JM, Paterson Y. Presentation of a horse cytochrome c peptide by multiple H-2b class I major histocompatibility complex (MHC) molecules to C57BL/6- and bm1-derived cytotoxic T lymphocytes: presence of a single MHC anchor residue may confer efficient peptide-specific CTL recognition. Eur J Immunol. 1994 Sep; 24(9):2141-9.
    View in: PubMed
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