- University of Michigan Medical School (MD-2000)
- Surgery Branch, National Cancer Institute (2000-2006)
- Johns Hopkins University School of Medicine (2006-2007)
- National Institute of Allergy and Infectious Diseases (2006-present)
- Johns Hopkins University School of Arts & Sciences (2010-present)
Laboratory of Immunology and Tumor Immunotherapy
Because many tumor antigens are self-antigens, T cell responses to tumor antigens may be impaired by previous exposure to the antigens in the host. Ergo, there is a strong need to study authentic self-antigens that are also tumor antigens if preclinical studies are to be translated to humans. Our long-term goal is to understand how to break self-tolerance to tumor antigens and how to maintain tumor immunity through immunological memory.
The Antony lab is interested in developing novel and potent immunotherapies that use the immune system to fight cancer. In 2010, we showed for the first time that tumor-specific CD4+ T cells can be cytolytic and kill cancer cells directly.
Lab Techniques and Equipment
- Nano drop 1000 instrument
- Cell Sorting by magnetic beads
- Adoptive Cell Transfer
- Cytokine Therapies
- CD4+ and CD8+ T Cell culture
- TCR Transgenic Mouse models of cancer
Grants and Contracts:
- K22 NCI Career Transition Grant, 2008-2011
- Melanoma Research Foundation Career Award, 2008-2010
- American Cancer Society Pilot Grant, 2010-2011
- DOD, Cancer Idea Award, 2011-2011
- Harold Lloyd Charitable Trust, 2012-2014
- DOD, PRCRP PostDoc Visionary Award for Stephen Goding, Ph.D. 2012-2014
eBioscience Cynthia Chambers Award, American Association of Immunologists, 2010
Antony PA, Yang H, Fan YY, et al. Altered Expression of Intraepithelial Lymphocyte (IEL) Keratinocyte Growth Factor (KGF) mRNA in the Mouse. Gastroenterology 118 (4): 658 Part 1 Suppl. 2 April 2000.
Kiristioglu I, Antony PA, Fan Y, Forbush B, Mosley RL, Yang H, Teitelbaum DH. Total Parental Nutrition-Associated Changes in Mouse Intestinal Intraepithelial Lymphocytes. Digestive Diseases and Sciences. Vol. 47, No. 5 May 2000.
Yang H, Kiritioglu I, Fan Y, Forbush B, Bishiop DK, Antony PA, Zhou H, Teitelbaum DH. Interferon-gamma expression by intraepithelial lymphocytes results in a loss of epithelial barrier function in a mouse model of total parenteral nutrition. Ann Surg. 2002 Aug;236(2):226-34.
Restifo NP, Antony PA, Finkelstein SE et al. Assumptions of the tumor 'escape' hypothesis. Semin Cancer Biol. 2002 Feb;12(1):81-6.
Antony PA and Restifo NP. Do CD4+CD25+ immunoregulatory T cells hinder tumor immunotherapy? J Immunother. 2002 May-Jun;25(3):202-6.
Overwijk WW, Theoret MR, Finkelstein SE, Surman, DR, Antony PA et al. Tumor regression and autoimmunity after reversal of a functionally tolerant state of self-reactive CD8+ T Cells. J Exp Med. 2003 Aug 18;198(4):569-80.
Diaz LA Jr, Pai R, Endres J, Antony PA, Duzyj C, Bishu S, Morita Y, Fox DA. Xenogeneic cells and superantigen induce human T-cell activation in the absence of T-cell recognition of xenoantigen. J Lab Clin Med. 2003 Sep;142(3):149-57.
Klebanoff CA, Gattinoni L, Antony PA et al. IL-15 enhances the in vivo anti-tumor activity of tumor-reactive CD8+ T cells. Pro Natl Acad Sci U S A. 2004 Feb 17;101(7):1969-74.
Yang H, Antony PA, Wildhaber BE, Teitelbaum DH. Intestinal Intraepithelial Lymphocyte gd-T Cell-Derived Keratinocyte Growth Factor Modulates Epithelial Growth in the Mouse. J Immunol. 2004 Apr 1;172(7):4151-8.
Finkelstein SE, Heimann DM, Klebanoff CA, Antony PA et al. Bedside to Bench and Back Again: How animal models are guiding the development of new immunotherapies for cancer. J Leukoc Biol. 2004 Aug;76(2):333-7.
Klebanoff CA, Khong H, Antony PA, Palmer D, Restifo NP. Sinks, suppressors and antigen presenters: how lymphphodepletion enhances T cell-mediated tumor immunotherapy. Trends Immunol. 2005 Feb;26(2):111-7.
Antony PA, Piccirillo CA, Akpinarli A et al. CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells. Cover Article: J Immunol. 2005 Mar 1;174(5):2591-601.
Antony PA, Restifo, NP. CD4+CD25+ T regulatory cells, immunotherapy of cancer, and interleukin-2. J of Immunother. 2005 Mar-Apr;28(2):120-8.
Klebanoff CA, Gattinoni L, Torabi P et al. Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells. Proc Natl Acad Sci U S A. 2005 Jul 5:102(27):9571-6.
Gattinoni L, Klebanoff CA, Finkelstein SE, Antony PA et al. Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J Exp Med. 2005 Oct 3;202(7):907-12.
Antony PA, Paulos C, Ahmadzadeh M, Akpinarli A et al. Interleukin-2-dependent mechanisms of tolerance and immunity in vivo. J Immunol. 2006 May 1;176(9):5255-66.
Gattinoni L, Ranganathan A, Surman DR, Palmer DP, Antony PA et al. CTLA-4 dysregulation of self/tumor-reactive CD8+ T cell function is CD4+ T cell-dependent. Blood. 2006 Aug 1.
Ahmadzadeh MA, Antony PA, Rosenberg SA. IL-2 and IL-15 each mediate de novo induction of FOXP3 expression in human tumor antigen-specific CD8 T cells. J Immunother. 2007 Apr;30(3):294-302.
Paulos CM, Wrzesinski C, Kaiser A, Hinrichs CS, Chieppa M, Cassard L, Palmer DC, Boni A, Muranski P, Yu Z, Gattinoni L, Antony PA, Rosenberg SA, and Restifo NP.Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via Toll-like receptor 4 signaling. JCI. August 2007.
Paulos, CM, Andrew Kaiser, Claudia Wrzesinski, Christian S. Hinrichs, Lydie Cassard, Andrea Boni, Pawel Muranski, Luis Sanchez-Perez, Douglas C. Palmer, Zhiya Yu, Antony PA, Luca Gattinoni, Steven A Rosenberg and Nicholas P. Restifo. Toll-like Receptors in Tumor Immunotherapy. Clinical Cancer Research.
Muranski PM*, Boni, A*, Antony PA*, Irvine K*, et al. Adoptive Transfer of Tumor-reactive Th17 CD4+ T cells are capable of inducing potent anti-tumor immunity. Blood, March 2008.
Xie, Y., Akpinarli, A., Maris, C., Lane, M., Hipkiss, E., Kwon, E-M., Muranski, P., Restifo, NP., Antony, PA. Naïve tumor-specific CD4+ T cells differentiaited in vivo eradicate established melanoma. Journal of Experimental Medicine. 2010.
Quezada, S., Simpson, T., Peggs, K., Mergoub, T, Muranksi, P., Antony, P.A., Restifo, N., Allison, JP. Tumor-reactive CD4+ T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. Journal of Experimental Medicine. 2010.
Rausch MP, Irvine KR, Antony PA, Restifo NP, Cresswell P, Hastings KT. GILT accelerates autoimmunity to the melanoma antigen tyrosinase-related protein 1. J Immunol. 2010 Sep 1;185(5):2828-35. Epub 2010 Jul 28.
Muranski P, Borman ZA, Kerkar SP, Klebanoff CA, Ji Y, Sanchez-Perez L, Sukumar M, Reger RN, Yu Z, Kern SJ, Roychoudhuri R, Ferreyra GA, Shen W, Durum SK, Feigenbaum L, Palmer DC, Chan C, Antony PA, Laurence A, Danner RL, Gattinoni L and Restifo NP. Th17-derived memory cells are long-lived and retain a stem cell-like molecular signature. Immunity 2011.
Jensen SM, Twitty CG, Maston LD, Antony PA, Lim M, Hu HM, Petrausch U, Restifo NP, Fox BA. Increased frequency of suppressive regulatory T cells and T cell-mediated antigen loss results in murine melanoma recurrence. J Immunol. 2012 Jul 15;189(2):767-76.
Goding SR, Wilson KA, Xie Y, Harris KM, Baxi A, Akpinarli A, Fulton A, Tamada K, Strome SE and Antony PA. Restoring immune function of tumor-specific CD4+ T cells during recurrence of melanoma. J Immunol. 2013 May 1;190(9)