Co-Director, Neuroblastoma Program
Department of Pediatrics
Center for Cell and Gene Therapy
Texas Children’s Cancer Center
Baylor College of Medicine
1102 Bates St., Suite 1760.06
Houston, TX 77030
About Leonid Metelitsa, MD, PhD
Dr. Leonid Metelitsa’s research is focused on understanding the role of Vα24-invariant Natural Killer T cells (NKTs) in tumor immunity. Dr. Metelitsa’s laboratory has published a series of high-impact papers that revealed the mechanism of NKT cell localization to the tumor site and their interaction with other cells in the tumor microenvironment. In one of these studies, they identified the mechanism by which aggressive neuroblastomas escape from NKT cell control (L. Song et al., J. Clin. Invest. 2007). In another, they discovered a novel mechanism by which NKT cell attack tumor-associated macrophages and mediate indirect anti-tumor activity in solid tumors (L. Song et al., J. Clin. Invest., 2009). In the next step toward understanding the role of NKT cells in the tumor microenvironment, Metelitsa’s lab discovered a general mechanism by which tumor-induced hypoxia neutralizes NKT-cell function and rescues tumor-supportive macrophages from the NKT-cell attack (D. Liu et al., J. Clin. Invest. 2012).
Dr. Metelitsa’s research spans the spectrum from the basic mechanisms of disease to the development of new therapies for children with cancer. To this end, he and his colleagues have developed a novel immunotherapeutic strategy using ex-vivo expanded NKT cells that are genetically modified with a neuroblastoma-specific chimeric antigen receptor (CAR) for targeting both tumor cells and tumor-supportive macrophages (A. Heczey et al., Blood, 2014). In another project, they developed a novel Salmonella-based cancer vaccine platform with the use of NKT ligands as adjuvants. They demonstrated that such vaccines have potent anti-tumor activity in mice with formation of protective memory (X. Xu et al., Canc. Res., 2014).
Postdoctoral Research Fellowship, Children’s Hospital Los Angeles, University of Southern California (mentor: Robert C. Seeger, MD), Los Angeles, CA
Ph.D. and Clinical Fellowship, N.N. Blokhin Memorial Cancer Research Center of Russian Academy of Medical Sciences, Moscow, Russia
M.D., Tver State Medical Academy, Tver, Russia
Member, American Association of Immunologists (AAI)
Elected Member, American Society of Clinical Investigation (ASCI)
Member, American Society of Gene & Cell Therapy (ASGCT)
Clinical Special Interests
Va24-Ja18-invariant Natural Killer T (iNKT) cells
NKT-based immunotherapeutic strategies
- Xin Xu, Wael Abdel Halim Hegazy, Linjie Guo, Xiuhua Gao, Amy N. Courtney, Suhrab Kurbanov, Daofeng Liu, Gengwen Tian, Edwin R. Manuel, Don J. Diamond, Michael Hensel, and Leonid S. Metelitsa. Development of an Effective Cancer Vaccine Using Attenuated Salmonella and Type III Secretion System to Deliver Recombinant Tumor-Associated Antigens. Cancer Res, 2014 Nov 1;74(21):6260-70.
- Andras Heczey, Daofeng Liu, Gengwen Tian, Amy N. Courtney, Jie Wei, Ekaterina Marinova, Xiuhua Gao, Linjie Guo, Eric Yvon, John Hicks, Gianpietro Dotti, and Leonid S. Metelitsa. Invariant NKT Cells with Chimeric Antigen Receptor Provide a Novel Platform for Safe and Effective Cancer Immunotherapy. Blood, 2014, Oct 30;124(18):2824-33. Selected for the cover of Blood issue.
- Liu D, Song L, Brawley VS, Robison N, Wei J, Gao X, Ahmed NM, Asgharzadeh S, Metelitsa LS. Medullublastoma expresses CD1d and can be targeted for immunotherapy with NKT cells. Clin Immunol., 2013, 149 (2013) pp. 55-64.
- Liu D, Song L, Wei J, Courtney AN, Gao X, Marinova E, Guo G, Heczey A, Asgharzadeh S, Kim E, Dotti D, Metelitsa LS. IL-15 protects NKTs from inhibition by tumor-associated macrophages and enhances anti-metastatic activity. J. Clin. Invest., 2012, 122(6):2221-33
- Metelitsa LS. Anti-tumor potential of type-I NKT cells against CD1d-positive and CD1d-negative tumors in humans. Clin Immunol. 2011 Aug; 140(2):119-29.
- Xiong G, Husseiny MI, Song L, Erdreich-Epstein A, Shackleford GM, Seeger RC, Jackel D, Hensel M, Metelitsa LS. Novel cancer vaccine based on genes of Salmonella pathogenicity Island 2. Int. J. Cancer. 2010 Jun 1; 126(11):2622-34.
- Song L, Asgharzadeh S, Salo S, Engel K, Sposto R, Ara T, Silverman AM, DeClerck YA, Seeger RC, Metelitsa LS. Natural Killer T cells mediate anti-tumor activity via killing of tumor-associated macrophages. J. Clin. Invest. 119(6):1524-36. Highlight in Nat. Rev. Immun. 2009; 9(6), p.388.
- Song L, Ara T, Wu H, Woo C, Reynolds CP, Seeger RC, DeClerck YA, Thiele CJ, Sposto R, Metelitsa LS. MYCN negatively regulates localization of Natural Killer T cells to the site of disease in neuroblastoma. J. Clin. Invest. 2007; 117(9):2702-12.
- Baev DV, Peng X, Song L, Barnhart JR, Crooks GM, Weinberg KI, Metelitsa LS. Distinct Homeostatic Requirements of CD4+ and CD4- Subsets of Vα24-invariant Natural Killer T cells in Humans. Blood. 2004 Dec 15; 104(13):4150-4160.
- Metelitsa LS, Wu H, Wang H, Yang Y, Warsi Z, Asgharzadeh S, Shimada H, Groshen S, Wilson SB, Seeger RC. Natural Killer T Cells Infiltrate Human Neuroblastomas Expressing the Chemokine CCL2. J Exp Med. 2004 May 3;199(9):1213-1221.
- Metelitsa LS, Weinberg KI, Emanuel PD, Seeger RC. CD1d provides a new target for immunotherapy of myeloid leukemia. Leukemia. 2003 Jun;17(6):1068-1077.
- Metelitsa LS, Naidenko OV, Kant A, Wu H, Loza MJ, Perussia B, Kronenberg M, Seeger RC. Human NKT Cells Mediate Anti-Tumor Cytotoxicity Directly by Recognizing Target Cell CD1d with Bound Ligand or Indirectly by Producing IL-2 to Activate NK Cells. J. Immunol. 2001; 167(6):3114-3122.