Targeting cancer stem cells by using chimeric antigen receptor-modified T cells: a potential and curable approach for cancer treatment

Yelei Guo, Kaichao Feng, Yao Wang, Weidong Han

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Protein Cell ›› 2018, Vol. 9 ›› Issue (6) : 516-526. DOI: 10.1007/s13238-017-0394-6
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Targeting cancer stem cells by using chimeric antigen receptor-modified T cells: a potential and curable approach for cancer treatment

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Abstract

Cancer stem cells (CSCs), a subpopulation of tumor cells, have self-renewal and multi-lineage differentiation abilities that play an important role in cancer initiation, maintenance, and metastasis. An accumulation of evidence indicates that CSCs can cause conventional therapy failure and cancer recurrence because of their treatment resistance and self-regeneration characteristics. Therefore, approaches that specifically and efficiently eliminate CSCs to achieve a durable clinical response are urgently needed. Currently, treatments with chimeric antigen receptor-modified T (CART) cells have shown successful clinical outcomes in patients with hematologic malignancies, and their safety and feasibility in solid tumors was confirmed. In this review, we will discuss in detail the possibility that CART cells inhibit CSCs by specifically targeting their cell surface markers, which will ultimately improve the clinical response for patients with various types of cancer. A number of viewpoints were summarized to promote the application of CSC-targeted CART cells in clinical cancer treatment. This review covers the key aspects of CSC-targeted CART cells against cancers in accordance with the premise of the model, from bench to bedside and back to bench.

Keywords

cancer stem cells / chimeric antigen receptor / immunotherapy / translational medicine / response evaluation criterion

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Yelei Guo, Kaichao Feng, Yao Wang, Weidong Han. Targeting cancer stem cells by using chimeric antigen receptor-modified T cells: a potential and curable approach for cancer treatment. Protein Cell, 2018, 9(6): 516‒526 https://doi.org/10.1007/s13238-017-0394-6

References

[1]
Ades F, Yamaguchi N (2015) WHO, RECIST, and immune-related response criteria: is it time to revisit pembrolizumab results? Ecancermedicalscience 9:604
CrossRef Google scholar
[2]
Ahmed N, Brawley VS, Hegde M (2015) Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor-modified Tcells for the immunotherapy of HER2-positive sarcoma. J Clin Oncol 33:1688–1696
CrossRef Google scholar
[3]
Alamgeer M, Peacock CD, Matsui W (2013) Cancer stem cells in lung cancer: Evidence and controversies. Respirology 18:757–764
CrossRef Google scholar
[4]
Al-Hajj M, Wicha MS, Benito-Hernandez A (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988
CrossRef Google scholar
[5]
Ang W, Li Z, Chi Z (2017) Intraperitoneal immunotherapy with T cells stably and transiently expressing anti-EpCAM CAR in xenograft models of peritoneal carcinomatosis. Oncotarget.
CrossRef Google scholar
[6]
Baba T, Convery PA, Matsumura N (2009) Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells. Oncogene 28:209–218
CrossRef Google scholar
[7]
Bakalova R, Ohba H, Zhelev Z (2004) Quantum dots as photosensitizers? Nat Biotechnol 22:1360–1361
CrossRef Google scholar
[8]
Bidlingmaier S, Zhu X, Liu B (2008) The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells. J Mol Med (Berl). 86:1025–1032
CrossRef Google scholar
[9]
Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737
CrossRef Google scholar
[10]
Bruce WR, Van Der Gaag HA (1963) Quantitative assay for the number of murine lymphoma cells capable of proliferation in vivo. Nature 199:79–80
CrossRef Google scholar
[11]
Budde LE, Berger C, Lin Y (2013) Combining a CD20 chimeric antigen receptor and an inducible caspase 9 suicide switch to improve the efficacy and safety of T cell adoptive immunotherapy for lymphoma. PLoS ONE 8:e82742
CrossRef Google scholar
[12]
Chao MP, Tang C, Pachynski RK (2011a) Extranodal dissemination of non-Hodgkin lymphoma requires CD47 and is inhibited by anti-CD47 antibody therapy. Blood 118:4890–4901
CrossRef Google scholar
[13]
Chao MP, Alizadeh AA, Tang C (2011b) Therapeutic antibody targeting of CD47 eliminates human acute lymphoblastic leukemia. Cancer Res 71:1374–1384
CrossRef Google scholar
[14]
Chen Y,Song J, Jiang Y (2015) Predictive value of CD44 and CD24 for prognosis and chemotherapy response in invasive breast ductal carcinoma. Int J Clin Exp Pathol 8:11287–11295
[15]
Collins AT, Berry PA, Hyde C (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946–10951
CrossRef Google scholar
[16]
Corbeil D, Marzesco AM, Wilsch-Brauninger M (2010) The intriguing links between prominin-1 (CD133), cholesterol-based membrane microdomains, remodeling of apical plasma membrane protrusions, extracellular membrane particles, and (neuro) epithelial cell differentiation. FEBS Lett 584:1659–1664
CrossRef Google scholar
[17]
Dai H, Zhang W, Li X (2015) Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia. Oncoimmunology 4:e1027469
CrossRef Google scholar
[18]
Deng Z, Wu Y, Ma W (2015) Adoptive T-cell therapy of prostate cancer targeting the cancer stem cell antigen EpCAM. BMC Immunol 16:1
CrossRef Google scholar
[19]
Dragu DL, Necula LG, Bleotu C (2015) Therapies targeting cancer stem cells: Current trends and future challenges. World J Stem Cells 26:1185–1201
[20]
Edris B, Weiskopf K, Volkmer AK (2012) Antibody therapy targeting the CD47 protein is effective in a model of aggressive metastatic leiomyosarcoma. Proc Natl Acad Sci USA 109:6656–6661
CrossRef Google scholar
[21]
Feldmann G, Dhara S, Fendrich V (2007) Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combinationtherapy in solid cancers. Cancer Res 67:2187–2196
CrossRef Google scholar
[22]
Feng K, Guo Y, Dai H (2016) Chimeric antigen receptormodified T cells for the immunotherapy of patients with EGFRexpressing advanced relapsed/refractory non-small cell lung cancer. Sci China Life Sci 59:468–479
CrossRef Google scholar
[23]
Feng K, Guo Y, Liu Y(2017) Cocktail treatment with EGFRspecific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma. J Hematol Oncol 10:4
CrossRef Google scholar
[24]
Focosi D, Bestagno M, Burrone O (2010) CD57+ T lymphocytes and functional immune deficiency. J Leukoc Biol 87:107–116
CrossRef Google scholar
[25]
Frank NY, Schatton T, Frank MH (2010) The therapeutic promise of the cancer stem cell concept. J Clin Invest 120:41–50
CrossRef Google scholar
[26]
Fukuda K, Saikawa Y, Ohashi M (2009) Tumor initiating potential of side population cells in human gastric cancer. Int J Oncol 34:1201–1207
[27]
Garfall AL, Maus MV, Hwang WT (2015) Chimeric antigen receptor Tcells against CD19 for multiple myeloma. N Engl J Med 373:1040–1047
CrossRef Google scholar
[28]
Ginestier C, Hur MH, Charafe-Jauffret E (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1:555–567
CrossRef Google scholar
[29]
Gires O, Klein CA, Baeuerle PA (2009) On the abundance of EpCAM on cancer stem cells. Nat Rev Cancer 9:143
CrossRef Google scholar
[30]
Grada Z, Hegde M, Byrd T (2013) TanCAR: a novel bispecific chimeric antigen receptor for cancer immunotherapy. Mol Ther Nucleic Acids 2:e105
CrossRef Google scholar
[31]
Gross G, Waks T, Eshhar Z (1989) Expression of immunoglobulin-Tcell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci USA 86:10024–10028
CrossRef Google scholar
[32]
Grupp SA, Kalos M, Barrett D (2013) Chimeric antigen receptormodified T cells for acute lymphoid leukemia. N Engl J Med 368:1509–1518
CrossRef Google scholar
[33]
Gupta PB, Chaffer CL, Weinberg RA (2009) Cancer stem cells: mirage or reality? Nat Med 15:1010–1012
CrossRef Google scholar
[34]
Hemmati HD, Nakano I, Lazareff JA (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA 100:15178–15183
CrossRef Google scholar
[35]
Hibi K, Sakata M, Kitamura YH (2010) Demethylation of the CD133 gene is frequently detected in early gastric carcinoma. Anticancer Res 30:1201–1203
[36]
Hodi FS, O’Day SJ, McDermott DF (2010) Improved survivalwith ipilimumab in patientswithmetastaticmelanoma. N Engl J Med 363:711–723
CrossRef Google scholar
[37]
Hong IS, Jang GB, Lee HY (2015) Targeting cancer stem cells by using the nanoparticles. Int J Nanomed 10(Spec Iss):251–260
[38]
Hoos A, Eggermont AM, Janetzki S (2010) Improved endpoints for cancer immunotherapy trials. J Natl Cancer Inst 102:1388–1397
CrossRef Google scholar
[39]
Hoos A, Wolchok JD, Humphrey RW (2015) CCR 20th anniversary commentary: immune-related response criteria-capturing clinical activity in immuno-oncology. Clin Cancer Res 21:4989–4991
CrossRef Google scholar
[40]
Jain A, Jain SK (2008) In vitro and cell uptake studies for targeting of ligand anchored nanoparticles for colon tumors. Eur J Pharm Sci 35:404–416
CrossRef Google scholar
[41]
Jain A, Jain SK, Ganesh N (2010) Design and development of ligand-appended polysaccharidic nanoparticles for the delivery of oxaliplatin in colorectal cancer. Nanomedicine 6:179–190
CrossRef Google scholar
[42]
Jensen MC, Riddell SR (2015) Designing chimeric antigen receptors to effectively and safely target tumors. Curr Opin Immunol 33:9–15
CrossRef Google scholar
[43]
Julien S,Merino-Trigo A, Lacroix L (2012) Characterization of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer. Clin Cancer Res 18(19):5314–5328
CrossRef Google scholar
[44]
Kastan MB, Schlaffer E, Russo JE (1990) Direct demonstration of elevated aldehyde dehydrogenase in human hematopoietic progenitor cells. Blood 75:1947–1950
[45]
Kershaw MH, Westwood JA, Darcy PK (2013) Gene-engineered T cells for cancer therapy. Nat Rev Cancer 13:525–541
CrossRef Google scholar
[46]
Khaleghi S, Rahbarizadeh F, Ahmadvand D (2012) A caspase 8-based suicide switch induces apoptosis in nanobody-directed chimeric receptor expressing T cells. Int J Hematol 95:434–444
CrossRef Google scholar
[47]
Khan N, Mukhtar H (2015) Dietary agents for prevention and treatment of lung cancer. Cancer Lett 359:155–164
CrossRef Google scholar
[48]
Kim D, Wang J, Willingham SB (2012) Anti-CD47 antibodies promote phagocytosis and inhibit the growth of human myeloma cells. Leukemia 26:2538–2545
CrossRef Google scholar
[49]
Kim MS, Ma JS, Yun H (2015) Redirection of genetically engineered CAR-T cells using bifunctional small molecules. J Am Chem Soc 137:2832–2835
CrossRef Google scholar
[50]
Kochenderfer JN, Dudley ME, Kassim SH (2015) Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol 33:540–549
CrossRef Google scholar
[51]
Lamers CH, Sleijfer S, van Steenbergen S (2013) Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation and management of on-target toxicity. Mol Ther 21:904–912
CrossRef Google scholar
[52]
Lapidot T, Sirard C, Vormoor J (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367:645–648
CrossRef Google scholar
[53]
Lee DW, Gardner R, Porter DL (2014) Current concepts in the diagnosis and management of cytokine release syndrome. Blood 124:188–195
CrossRef Google scholar
[54]
Li C, Heidt DG, Dalerba P (2007) Identification of pancreatic cancer stem cells. Cancer Res 67:1030–1037
CrossRef Google scholar
[55]
Lingala S, Cui YY, Chen X (2010) Immunohistochemical staining of cancer stem cell markers in hepatocellular carcinoma. Exp Mol Pathol 89:27–35
CrossRef Google scholar
[56]
Liu J, Jiang G (2006) CD44 and hematologic malignancies. Cell Mol Immunol 3:359–365
[57]
Lu JW, Chang JG, Yeh KT (2011) Overexpression of Thy1/CD90 in human hepatocellular carcinoma is associated with HBV infection and poor prognosis. Acta Histochem 113:833–838
CrossRef Google scholar
[58]
Ma S, Chan KW, Hu L (2007) Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology 132:2542–2556
CrossRef Google scholar
[59]
Ma ZL, Chen YP, Song JL (2015) Knock-down of CD24 inhibits proliferation, invasion and sensitizes breast cancer MCF-7 cells to tamoxifen in vitro. Eur Rev Med Pharmacol Sci 19:2394–2399
[60]
Majeti R, Chao MP, Alizadeh AA (2009) CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell 138:286–299
CrossRef Google scholar
[61]
Marchitti SA, Brocker C, Stagos D (2008) Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily. Expert Opin Drug Metab Toxicol 4:697–720
CrossRef Google scholar
[62]
Maude SL, Frey N, Shaw PA (2014) Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 371:1507
CrossRef Google scholar
[63]
Mitra M, Kandalam M, Verma RS (2010) Genome-wide changes accompanying the knockdown of Ep-CAM in retinoblastoma. Mol Vis 16:828–842
[64]
Morgan RA, Yang JC, Kitano M (2010) Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther 18:843–851
CrossRef Google scholar
[65]
Munz M, Baeuerle PA, Gires O (2009) The emerging role of EpCAM in cancer and stem cell signaling. Cancer Res 69:5627–5629
CrossRef Google scholar
[66]
Naujokat C (2012) Targeting human cancer stem cells with monoclonal antibodies. J Clin Cell Immunol S5:7
CrossRef Google scholar
[67]
O’Brien CA, Pollett A, Gallinger S (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445:106–110
CrossRef Google scholar
[68]
Ogura E, Senzaki H, Yoshizawa K (1998) Immunohistochemical localization of epithelial glycoprotein EGP-2 and carcinoembryonic antigen in normal colonic mucosa and colorectal tumors. Anticancer Res 18:3669–3675
[69]
Osta WA, Chen Y, Mikhitarian K (2004) EpCAM is overexpressed inbreast cancer and is a potential target for breast cancer gene therapy. Cancer Res 64:5818–5824
CrossRef Google scholar
[70]
Pan Q, Li Q, Liu S (2015) Concise review: targeting cancer stem cells using immunologic approaches. Stem Cells 33:2085–2092
CrossRef Google scholar
[71]
Porter DL, Levine BL, Kalos M (2011) Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 365:725–733
CrossRef Google scholar
[72]
Rege TA, Hagood JS (2006) Thy-1 as a regulator of cell-cell and cellmatrix interactions in axon regeneration, apoptosis, adhesion, migration, cancer, and fibrosis. FASEB J 20:1045–1054
CrossRef Google scholar
[73]
Reya T, Morrison SJ, Clarke MF (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111
CrossRef Google scholar
[74]
Ricci-Vitiani L, Lombardi DG, Pilozzi E (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445:111–115
CrossRef Google scholar
[75]
Rosfjord E, Lucas J, Li G (2014) Advances in patient-derived tumor xenografts: From target identification to predicting clinical response rates in oncology. Biochem Pharmacol 91(2):135–143
CrossRef Google scholar
[76]
Sadelain M, Brentjens R, Riviere I (2013) The basic principles of chimeric antigen receptor design. Cancer Discov 3:388–398
CrossRef Google scholar
[77]
Salomon J, Goulet O, Canioni D (2014) Genetic characterization of congenital tufting enteropathy: epcam associated phenotype and involvement of SPINT2 in the syndromic form. Hum Genet 133:299–310
CrossRef Google scholar
[78]
Savona MR, Malcovati L, Komrokji R (2015) An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (mds/mpn) in adults. Blood 125:1857–1865
CrossRef Google scholar
[79]
Schmidt M, Scheulen ME, Dittrich C (2010) An open-label, randomized phase II study of adecatumumab, a fully human anti-EpCAM antibody, as monotherapy in patients with metastatic breast cancer. Ann Oncol 21:275–282
CrossRef Google scholar
[80]
Shigdar S, Lin J, Yu Y, Pastuovic M (2011) RNA aptamer against a cancer stem cell marker epithelial cell adhesion molecule. Cancer Sci 102:991–998
CrossRef Google scholar
[81]
Shmelkov SV, St Clair R, Lyden D (2005) AC133/CD133/Prominin-1. Int J Biochem Cell Biol 37:715–719
CrossRef Google scholar
[82]
Skubitz AP, Taras EP, Boylan KL (2013) Targeting CD133 in an in vivo ovarian cancer model reduces ovarian cancer progression. Gynecol Oncol 130:579–587
CrossRef Google scholar
[83]
Smith LM, Nesterova A, Ryan MC (2008) CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers. Br J Cancer 99:100–109
CrossRef Google scholar
[84]
Song G, Liao X, Zhou L (2004) HI44a, an anti-CD44 monoclonal antibody, induces differentiation and apoptosis of human acute myeloid leukemia cells. Leuk Res 28:1089–1096
CrossRef Google scholar
[85]
Song Y, Zhu Z, An Y (2013) Selection of DNA aptamers against epithelial cell adhesion molecule for cancer cell imaging and circulating tumor cell capture. Anal Chem 85:4141–4149
CrossRef Google scholar
[86]
Stewart BW, Wild C, International Agency for Research on Cancer and World Health Organization (2014) World cancer report 2014. International Agency for Research on Cancer WHO Press, Lyon, France/Geneva, Switzerland
[87]
Strioga M, Pasukoniene V, Characiejus D (2011) CD8+ CD28- and CD8+CD57+ T cells and their role in health and disease. Immunology 134:17–32
CrossRef Google scholar
[88]
Su YJ, Lin WH, Chang YW (2015) Polarized cell migration induces cancer type-specific CD133/integrin/Src/Akt/GSK3β/β-catenin signaling required for maintenance of cancer stem cell properties. Oncotarget 6:38029–38045
CrossRef Google scholar
[89]
Sukowati CH, Anfuso B, Torre G (2013) The expression of CD90/Thy-1 in hepatocellular carcinoma: an in vivo and in vitro study. PLoS ONE 8:e76830
CrossRef Google scholar
[90]
Swaminathan SK, Roger E, Toti U (2013) CD133-targeted paclitaxel delivery inhibits local tumor recurrence in a mouse model of breast cancer. J Control Release 171:280–287
CrossRef Google scholar
[91]
Tang KH, Dai YD, Tong M (2013) A CD90(+) tumor-initiating cell population with an aggressive signature and metastatic capacity in esophageal cancer. Cancer Res 73:2322–2332
CrossRef Google scholar
[92]
Till BG, Jensen MC, Wang J (2012) CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results. Blood 119:3940–3950
CrossRef Google scholar
[93]
Van der Gun BT, Melchers LJ, Ruiters MH (2010) EpCAM in carcinogenesis: the good, the bad or the ugly. Carcinogenesis 31:1913–1921
CrossRef Google scholar
[94]
Visus C, Wang Y, Lozano-Leon A (2011) Targeting ALDH bright human carcinoma-initiating cells with ALDH1A1-Specific CD8+ T cells. Clin Cancer Res 17:6174–6184
CrossRef Google scholar
[95]
Visvader JE, Lindeman GJ (2008) Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 8:755–768
CrossRef Google scholar
[96]
Wang L, Su W, Liu Z (2012) CD44 antibody-targeted liposomal nanoparticles for molecular imaging and therapy of hepatocellular carcinoma. Biomaterials 33:5107–5114
CrossRef Google scholar
[97]
Wang Y, Zhang WY, Han QW (2014) Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptormodified T cells. Clin Immunol 155:160–175
CrossRef Google scholar
[98]
Wang QS, Wang Y, Lv HY (2015a) Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia. Mol Ther 23:184–191
CrossRef Google scholar
[99]
Wang X, Liu Y, Zhou K (2015b) Isolation and characterization of CD105+/CD90+ subpopulation in breast cancer MDA-MB-231 cell line. Int J Clin Exp Pathol 8:5105–5112
[100]
Willingham SB, Volkmer JP, Gentles AJ (2012) The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc Natl Acad Sci USA 109:6662–6667
CrossRef Google scholar
[101]
Wolchok JD, Hoos A, O’Day S (2009) Guidelines for the evaluation of immune therapy activity in solid tumors: immunerelated response criteria. Clin Cancer Res 15:7412–7420
CrossRef Google scholar
[102]
Woo SR, Oh YT, An JY (2015) Glioblastoma specific antigens, GD2 and CD90, are not involved in cancer stemness. Anat Cell Biol 48:44–53
CrossRef Google scholar
[103]
Wu RC, Liu S, Chacon JA (2012) Detection and characterization of a novel subset of CD8(+)CD57(+) T cells in metastatic melanoma with an incompletely differentiated phenotype. Clin Cancer Res 18:2465–2477
CrossRef Google scholar
[104]
Wu CY, Roybal KT, Puchner EM (2015) Remote control of therapeutic T cells through a small molecule-gated chimeric receptor. Science 350:4077
CrossRef Google scholar
[105]
Yamashita T, Wang XW (2013) Cancer stem cells in the development of liver cancer. J Clin Invest 123:1911–1918
CrossRef Google scholar
[106]
Yee C, Thompson JA, Byrd D (2002) Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc Natl Acad Sci USA 99:16168–16173
CrossRef Google scholar
[107]
Yi JM, Tsai HC, Glöckner SC (2008) Abnormal DNA methylation of CD133 in colorectal and glioblastoma tumors. Cancer Res 68:8094–8103
CrossRef Google scholar
[108]
Yin AH, Miraglia S, Zanjani ED (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 90:5002–5012
[109]
Zhang Q, Shi S, Yen Y (2010) A subpopulation of CD133(+) cancer stem-like cells characterized in human oral squamous cell carcinoma confer resistance to chemotherapy. Cancer Lett 289:151–160
CrossRef Google scholar
[110]
Zhang C, Zhou C, Wu XJ (2014a) Human CD133-positive hematopoietic progenitor cells initiate growth and metastasis of colorectal cancer cells. Carcinogenesis 35:2771–2777
CrossRef Google scholar
[111]
Zhang YH, Wang ZY, Hao FYl (2014b) Cluster of differentiation 24 monoclonal antibody induces apoptosis in the osteosarcoma cells. Eur Rev Med Pharmacol Sci 18:2038–2041
[112]
Zhao L, Yang Y, Zhou P (2015) Targeting CD133 high colorectal cancer cells in vitro and in vivo with an asymmetric bispecific antibody. J Immunother 38:217–228
CrossRef Google scholar
[113]
Zhu J, Thakolwiboon S, Liu X (2014) Overexpression of CD90 (Thy-1) in pancreatic adenocarcinoma present in the tumor microenvironment. PLoS ONE 9:e115507
CrossRef Google scholar
[114]
Zhu X, Prasad S, Gaedicke Sl (2015) Patient-derived glioblastoma stem cells are killed by CD133-specific CAR T cells but induce the T cell aging marker CD57. Oncotarget 6:171–184
CrossRef Google scholar

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