International Journal of Hematological Disorders
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International Journal of Hematological Disorders. 2015, 2(2), 39-42
DOI: 10.12691/ijhd-2-2-3
Open AccessReview Article

Immunotherapy Targeting Leukemia Stem Cells

Maiko Matsushita1,

1Division of Clinical Physiology and Therapeutics, Keio University Faculty of Pharmacy, Tokyo, Japan

Pub. Date: July 22, 2015

Cite this paper:
Maiko Matsushita. Immunotherapy Targeting Leukemia Stem Cells. International Journal of Hematological Disorders. 2015; 2(2):39-42. doi: 10.12691/ijhd-2-2-3

Abstract

Leukemia stem cells (LSCs) are considered to cause treatment failure and disease progression in leukemia patients. Although LSCs are rare, they are a quiescent population and so cannot be targeted by conventional therapies such as chemotherapy, targeted therapy, and radiotherapy. On the other hand, immunotherapy including hematopoietic stem cell transplantation could target LSCs regardless of cell cycle status. Identification of LSC-specific antigens is important for developing effective immunotherapies. Several antigens highly expressed in LSCs or on the surface of LSCs have been reported, and some of them have been found useful for eradication of LSCs. Cancer vaccines, adoptive T cell therapy, and antibody treatments to target these antigens are strategies expected to be used in the near future.

Keywords:
immunotherapy leukemia stem cells antigens

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]  Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105-111.
 
[2]  Kreso A and Dick JE. Evolution of the cancer stem cell model. Cell Stem Cell. 2014;14(3):275-291.
 
[3]  Chomel JC and Turhan AG. Chronic myeloid leukemia stem cells in the era of targeted therapies: resistance, persistence and long-term dormancy. Oncotarget. 2011;2(9):713-727.
 
[4]  Jorgensen HG and Holyoake TL. Characterization of cancer stem cells in chronic myeloid leukaemia. Biochem Soc Trans. 2007;35(Pt 5):1347-1351.
 
[5]  Maugeri-Sacca M, Vigneri P, De Maria R. Cancer stem cells and chemosensitivity. Clin Cancer Res. 2011;17(15):4942-4947.
 
[6]  Diehn M and Clarke MF. Cancer stem cells and radiotherapy: new insights into tumor radioresistance. J Natl Cancer Inst. 2006;98(24):1755-1757.
 
[7]  Tang M, Gonen M, Quintas-Cardama A, et al. Dynamics of chronic myeloid leukemia response to long-term targeted therapy reveal treatment effects on leukemic stem cells. Blood. 2011;118(6):1622-1631.
 
[8]  Rousselot P, Charbonnier A, Cony-Makhoul P, et al. Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. J Clin Oncol. 2014;32(5):424-430.
 
[9]  Ross DM, Branford S, Seymour JF, et al. Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood. 2013;122(4):515-522.
 
[10]  Mahon FX, Rea D, Guilhot J, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010;11(11):1029-1035.
 
[11]  Jenq RR and van den Brink MR. Allogeneic haematopoietic stem cell transplantation: individualized stem cell and immune therapy of cancer. Nat Rev Cancer. 2010;10(3):213-221.
 
[12]  Kolb HJ. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008;112(12):4371-4383.
 
[13]  Deol A and Lum LG. Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited. Cancer Treat Rev. 2010;36(7):528-538.
 
[14]  Michallet M. Allogeneic hematopoietic stem cell transplantations. Transfus Clin Biol. 2011;18(2):235-245.
 
[15]  Reddy P and Ferrara JL. Immunobiology of acute graft-versus-host disease. Blood Rev. 2003;17(4):187-194.
 
[16]  Zilberberg J, Feinman R, Korngold R. Strategies for the identification of T cell-recognized tumor antigens in hematological malignancies for improved graft-versus-tumor responses after allogeneic blood and marrow transplantation. Biol Blood Marrow Transplant. 2015;21(6):1000-1007.
 
[17]  Choi S and Reddy P. Graft-versus-host disease. Panminerva Med. 2010;52(2):111-124.
 
[18]  Cheever MA, Allison JP, Ferris AS, et al. The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res. 2009;15(17):5323-5337.
 
[19]  Inoue K, Ogawa H, Sonoda Y, et al. Aberrant overexpression of the Wilms tumor gene (WT1) in human leukemia. Blood. 1997;89(4):1405-1412.
 
[20]  Bergmann L, Miething C, Maurer U, et al. High levels of Wilms' tumor gene (wt1) mRNA in acute myeloid leukemias are associated with a worse long-term outcome. Blood. 1997;90(3):1217-1225.
 
[21]  Saito Y, Kitamura H, Hijikata A, et al. Identification of therapeutic targets for quiescent, chemotherapy-resistant human leukemia stem cells. Sci Transl Med. 2010;2(17):17ra9.
 
[22]  Saitoh A, Narita M, Watanabe N, et al. WT1 peptide vaccination in a CML patient: induction of effective cytotoxic T lymphocytes and significance of peptide administration interval. Med Oncol. 2010.
 
[23]  Hosen N, Maeda T, Hashii Y, et al. Vaccination strategies to improve outcome of hematopoietic stem cell transplant in leukemia patients: early evidence and future prospects. Expert Rev Hematol. 2014;7(5):671-681.
 
[24]  Oka Y, Udaka K, Tsuboi A, et al. Cancer immunotherapy targeting Wilms' tumor gene WT1 product. J Immunol. 2000;164(4):1873-1880.
 
[25]  Ochi T, Fujiwara H, Okamoto S, et al. Novel adoptive T-cell immunotherapy using a WT1-specific TCR vector encoding silencers for endogenous TCRs shows marked antileukemia reactivity and safety. Blood. 2011;118(6):1495-1503.
 
[26]  Gerber JM, Qin L, Kowalski J, et al. Characterization of chronic myeloid leukemia stem cells. Am J Hematol. 2011;86(1):31-37.
 
[27]  Matsushita M, Yamazaki R, Ikeda H, Kawakami Y. Preferentially expressed antigen of melanoma (PRAME) in the development of diagnostic and therapeutic methods for hematological malignancies. Leuk Lymphoma. 2003;44(3):439-444.
 
[28]  Yan M, Himoudi N, Basu BP, et al. Increased PRAME antigen-specific killing of malignant cell lines by low avidity CTL clones, following treatment with 5-Aza-2'-Deoxycytidine. Cancer Immunol Immunother. 2011;60(9):1243-1255.
 
[29]  Schneider V, Zhang L, Rojewski M, et al. Leukemic progenitor cells are susceptible to targeting by stimulated cytotoxic T cells against immunogenic leukemia-associated antigens [published online Apr 24 2015]. Int J Cancer. 2015.
 
[30]  Zhou H and Xu R. Leukemia stem cells: the root of chronic myeloid leukemia. Protein Cell. 2015;6(6):403-412.
 
[31]  Tosi D, Laghzali Y, Vinches M, et al. Clinical Development Strategies and Outcomes in First-in-Human Trials of Monoclonal Antibodies [published online May 26 2015]. J Clin Oncol. 2015.
 
[32]  Weiner GJ. Building better monoclonal antibody-based therapeutics. Nat Rev Cancer. 2015;15(6):361-370.
 
[33]  Deonarain MP, Kousparou CA, Epenetos AA. Antibodies targeting cancer stem cells: a new paradigm in immunotherapy? MAbs. 2009;1(1):12-25.
 
[34]  Gerber JM, Gucwa JL, Esopi D, et al. Genome-wide comparison of the transcriptomes of highly enriched normal and chronic myeloid leukemia stem and progenitor cell populations. Oncotarget. 2013;4(5):715-728.
 
[35]  Kobayashi CI, Takubo K, Kobayashi H, et al. The IL-2/CD25 axis maintains distinct subsets of chronic myeloid leukemia-initiating cells. Blood. 2014;123(16):2540-2549.
 
[36]  Herrmann H, Sadovnik I, Cerny-Reiterer S, et al. Dipeptidylpeptidase IV (CD26) defines leukemic stem cells (LSC) in chronic myeloid leukemia. Blood. 2014;123(25):3951-3962.
 
[37]  Hosen N, Park CY, Tatsumi N, et al. CD96 is a leukemic stem cell-specific marker in human acute myeloid leukemia. Proc Natl Acad Sci U S A. 2007;104(26):11008-11013.
 
[38]  Liu K, Zhu M, Huang Y, et al. CD123 and its potential clinical application in leukemias. Life Sci. 2015;122:59-64.
 
[39]  Gill S, Tasian SK, Ruella M, et al. Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. Blood. 2014;123(15):2343-2354.
 
[40]  Kikushige Y, Shima T, Takayanagi S, et al. TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells. Cell Stem Cell. 2010;7(6):708-717.
 
[41]  Ngiow SF, Teng MW, Smyth MJ. Prospects for TIM3-Targeted Antitumor Immunotherapy. Cancer Res. 2011;71(21):6567-6571.
 
[42]  Hertweck MK, Erdfelder F, Kreuzer KA. CD44 in hematological neoplasias. Ann Hematol. 2011;90(5):493-508.
 
[43]  Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med. 2006;12(10):1167-1174.
 
[44]  Bonardi F, Fusetti F, Deelen P, van Gosliga D, Vellenga E, Schuringa JJ. A proteomics and transcriptomics approach to identify leukemic stem cell (LSC) markers. Mol Cell Proteomics. 2013;12(3):626-637.
 
[45]  Kreutzman A, Juvonen V, Kairisto V, et al. Mono/oligoclonal T and NK cells are common in chronic myeloid leukemia patients at diagnosis and expand during dasatinib therapy. Blood. 2010;116(5):772-782.
 
[46]  Matsushita M, Tonegawa K, Mori T, et al. Detection of leukemia associated antigen-specific cytotoxic T cells in a patient with Philadelphia chromosome-positive leukemia during treatment with dasatinib. Leuk Lymphoma. 2014;55(3):722-724.
 
[47]  Dudley ME, Wunderlich JR, Yang JC, et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005;23(10):2346-57.
 
[48]  Bauer C, Hees C, Sterzik A, et al. Proapoptotoc and antiapoptotic proteins of the Bcl-2 family regulate sensitivity of pancreatic cancer cells toward gemcitabine and T-cell-mediated cytotoxicity. J Immunother. 2015;38(3):116-26.