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BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

T lymphocytes derived from human cord blood provide effective antitumor immunotherapy against a human tumor

Authors: Yong-Soo Lee, Tae-Sik Kim, Dong-Ku Kim

Published in: BMC Cancer | Issue 1/2011

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Abstract

Background

Although the graft-versus-tumor (GVT) effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation has been used as an effective adoptive immunotherapy, the antitumor effects of cord blood (CB) transplantation have not been well studied.

Methods

We established the animal model by transplantation of CB mononuclear cells and/or tumor cells into NOD/SCID mice. The presence of CB derived T cells in NOD/SCID mice or tumor tissues were determined by flow cytometric and immunohistochemical analysis. The anti-tumor effects of CB derived T cells against tumor was determined by tumor size and weight, and by the cytotoxicity assay and ELISPOT assay of T cells.

Results

We found dramatic tumor remission following transfer of CB mononuclear cells into NOD/SCID mice with human cervical tumors with a high infiltration of CD3+ T cells in tumors. NOD/SCID mice that receive neonatal CB transplants have reconstituted T cells with significant antitumor effects against human cervical and lung tumors, with a high infiltration of CD3+ T cells showing dramatic induction of apoptotic cell death. We also confirmed that T cells showed tumor specific antigen cytotoxicity in vitro. In adoptive transfer of CD3+ T cells into mice with pre-established tumors, we observed much higher antitumor effects of HPV-specific T cells by ELISPOT assays.

Conclusions

Our results show that CB derived T lymphocytes will be useful for novel immunotherapeutic candidate cells for therapy of several tumors in clinic.
Appendix
Available only for authorised users
Literature
1.
Bradley MB, Satwani P, Baldinger L, Morris E, van de Ven C, Del Toro G, Garvin J, George D, Bhatia M, Roman E, et al: Reduced intensity allogeneic umbilical cord blood transplantation in children and adolescent recipients with malignant and non-malignant diseases. Bone Marrow Transplant. 2007, 40 (7): 621-631. 10.1038/sj.bmt.1705785.CrossRefPubMed
2.
Kurtzberg J, Laughlin M, Graham ML, Smith C, Olson JF, Halperin EC, Ciocci G, Carrier C, Stevens CE, Rubinstein P: Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients. N Engl J Med. 1996, 335 (3): 157-166. 10.1056/NEJM199607183350303.CrossRefPubMed
3.
Wagner JE, Rosenthal J, Sweetman R, Shu XO, Davies SM, Ramsay NK, McGlave PB, Sender L, Cairo MS: Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease. Blood. 1996, 88 (3): 795-802.PubMed
4.
Amlot PL, Tahami F, Chinn D, Rawlings E: Activation antigen expression on human T cells. I. Analysis by two-colour flow cytometry of umbilical cord blood, adult blood and lymphoid tissue. Clin Exp Immunol. 1996, 105 (1): 176-182. 10.1046/j.1365-2249.1996.d01-722.x.CrossRefPubMedPubMedCentral
5.
Beck R, Lam-Po-Tang PR: Comparison of cord blood and adult blood lymphocyte normal ranges: a possible explanation for decreased severity of graft versus host disease after cord blood transplantation. Immunol Cell Biol. 1994, 72 (5): 440-444. 10.1038/icb.1994.65.CrossRefPubMed
6.
D'Arena G, Musto P, Cascavilla N, Di Giorgio G, Fusilli S, Zendoli F, Carotenuto M: Flow cytometric characterization of human umbilical cord blood lymphocytes: immunophenotypic features. Haematologica. 1998, 83 (3): 197-203.PubMed
7.
Han P, Hodge G, Story C, Xu X: Phenotypic analysis of functional T-lymphocyte subtypes and natural killer cells in human cord blood: relevance to umbilical cord blood transplantation. Br J Haematol. 1995, 89 (4): 733-740.CrossRefPubMed
8.
Garderet L, Dulphy N, Douay C, Chalumeau N, Schaeffer V, Zilber MT, Lim A, Even J, Mooney N, Gelin C, et al: The umbilical cord blood alphabeta T-cell repertoire: characteristics of a polyclonal and naive but completely formed repertoire. Blood. 1998, 91 (1): 340-346.PubMed
9.
Schelonka RL, Raaphorst FM, Infante D, Kraig E, Teale JM, Infante AJ: T cell receptor repertoire diversity and clonal expansion in human neonates. Pediatr Res. 1998, 43 (3): 396-402. 10.1203/00006450-199803000-00015.CrossRefPubMed
10.
Anderson LD, Mori S, Mann S, Savary CA, Mullen CA: Pretransplant tumor antigen-specific immunization of allogeneic bone marrow transplant donors enhances graft-versus-tumor activity without exacerbation of graft-versus-host disease. Cancer Res. 2000, 60 (20): 5797-5802.PubMed
11.
Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S, Negrin RS: CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med. 2003, 9 (9): 1144-1150. 10.1038/nm915.CrossRefPubMed
12.
Eibl B, Schwaighofer H, Nachbaur D, Marth C, Gachter A, Knapp R, Bock G, Gassner C, Schiller L, Petersen F, et al: Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer. Blood. 1996, 88 (4): 1501-1508.PubMed
13.
Ito M, Shizuru JA: Graft-vs.-lymphoma effect in an allogeneic hematopoietic stem cell transplantation model. Biol Blood Marrow Transplant. 1999, 5 (6): 357-368. 10.1016/S1083-8791(99)70012-1.CrossRefPubMed
14.
Feuerer M, Beckhove P, Bai L, Solomayer EF, Bastert G, Diel IJ, Pedain C, Oberniedermayr M, Schirrmacher V, Umansky V: Therapy of human tumors in NOD/SCID mice with patient-derived reactivated memory T cells from bone marrow. Nat Med. 2001, 7 (4): 452-458. 10.1038/86523.CrossRefPubMed
15.
Evans EM, Man S, Evans AS, Borysiewicz LK: Infiltration of cervical cancer tissue with human papillomavirus-specific cytotoxic T-lymphocytes. Cancer Res. 1997, 57 (14): 2943-2950.PubMed
16.
Ressing ME, van Driel WJ, Celis E, Sette A, Brandt MP, Hartman M, Anholts JD, Schreuder GM, ter Harmsel WB, Fleuren GJ, et al: Occasional memory cytotoxic T-cell responses of patients with human papillomavirus type 16-positive cervical lesions against a human leukocyte antigen-A *0201-restricted E7-encoded epitope. Cancer Res. 1996, 56 (3): 582-588.PubMed
17.
Livingston RB: Combined modality therapy of lung cancer. Clin Cancer Res. 1997, 3 (12 Pt 2): 2638-2647.PubMed
18.
Pilon-Thomas SA, Verhaegen ME, Mule JJ: Dendritic cell-based therapeutics for breast cancer. Breast Dis. 2004, 20: 65-71.CrossRefPubMed
19.
Srinivasan R, Van Epps DE: Specific active immunotherapy of cancer: potential and perspectives. Rev Recent Clin Trials. 2006, 1 (3): 283-292. 10.2174/157488706778250113.CrossRefPubMed
20.
Yan L, Hsu K, Beckman RA: Antibody-based therapy for solid tumors. Cancer J. 2008, 14 (3): 178-183. 10.1097/PPO.0b013e318172d71a.CrossRefPubMed
21.
Hagihara M, Gansuvd B, Ueda Y, Tsuchiya T, Masui A, Tazume K, Inoue H, Kato S, Hotta T: Killing activity of human umbilical cord blood-derived TCRValpha24(+) NKT cells against normal and malignant hematological cells in vitro: a comparative study with NK cells or OKT3 activated T lymphocytes or with adult peripheral blood NKT cells. Cancer Immunol Immunother. 2002, 51 (1): 1-8. 10.1007/s00262-001-0246-2.CrossRefPubMed
22.
Joshi AD, Clark EM, Wang P, Munger CM, Hegde GV, Sanderson S, Dave HP, Joshi SS: Immunotherapy of human neuroblastoma using umbilical cord blood-derived effector cells. J Neuroimmune Pharmacol. 2007, 2 (2): 202-212. 10.1007/s11481-006-9038-y.CrossRefPubMed
23.
Lin P, Lu YR, Zhang J, Wei YQ, Wang XJ, Li SF, Wang Q, Xiong ZJ, Ning QZ, Lei S, et al: Antitumor effect of lung cancer vaccine with umbilical blood dendritic cells in reconstituted SCID mice. Cancer Biother Radiopharm. 2008, 23 (3): 321-331. 10.1089/cbr.2008.0463.CrossRefPubMed
24.
Lovgren TR, Tarantolo SR, Evans C, Kuszynski CA, Joshi SS: Enhanced in vitro and in vivo cytotoxicity of umbilical cord blood cells against human breast cancer following activation with IL-15 and colony stimulating factors. In Vivo. 2002, 16 (6): 541-550.PubMed
25.
Knutson KL, Disis ML: Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol Immunother. 2005, 54 (8): 721-728. 10.1007/s00262-004-0653-2.CrossRefPubMed
26.
Hiramatsu H, Nishikomori R, Heike T, Ito M, Kobayashi K, Katamura K, Nakahata T: Complete reconstitution of human lymphocytes from cord blood CD34+ cells using the NOD/SCID/gammacnull mice model. Blood. 2003, 102 (3): 873-880. 10.1182/blood-2002-09-2755.CrossRefPubMed
27.
Yu Y, Hagihara M, Ando K, Gansuvd B, Matsuzawa H, Tsuchiya T, Ueda Y, Inoue H, Hotta T, Kato S: Enhancement of human cord blood CD34+ cell-derived NK cell cytotoxicity by dendritic cells. J Immunol. 2001, 166 (3): 1590-1600.CrossRefPubMed
28.
Hogan CJ, Shpall EJ, Keller G: Differential long-term and multilineage engraftment potential from subfractions of human CD34+ cord blood cells transplanted into NOD/SCID mice. Proc Natl Acad Sci USA. 2002, 99 (1): 413-418. 10.1073/pnas.012336799.CrossRefPubMedPubMedCentral
29.
van der Loo JC, Hanenberg H, Cooper RJ, Luo FY, Lazaridis EN, Williams DA: Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse as a model system to study the engraftment and mobilization of human peripheral blood stem cells. Blood. 1998, 92 (7): 2556-2570.PubMed
30.
Nakagawa M, Stites DP, Farhat S, Sisler JR, Moss B, Kong F, Moscicki AB, Palefsky JM: Cytotoxic T lymphocyte responses to E6 and E7 proteins of human papillomavirus type 16: relationship to cervical intraepithelial neoplasia. J Infect Dis. 1997, 175 (4): 927-931. 10.1086/513992.CrossRefPubMed
31.
Nimako M, Fiander AN, Wilkinson GW, Borysiewicz LK, Man S: Human papillomavirus-specific cytotoxic T lymphocytes in patients with cervical intraepithelial neoplasia grade III. Cancer Res. 1997, 57 (21): 4855-4861.PubMed
32.
Youde SJ, Dunbar PR, Evans EM, Fiander AN, Borysiewicz LK, Cerundolo V, Man S: Use of fluorogenic histocompatibility leukocyte antigen-A*0201/HPV 16 E7 peptide complexes to isolate rare human cytotoxic T-lymphocyte-recognizing endogenous human papillomavirus antigens. Cancer Res. 2000, 60 (2): 365-371.PubMed
33.
Haddad R, Guardiola P, Izac B, Thibault C, Radich J, Delezoide AL, Baillou C, Lemoine FM, Gluckman JC, Pflumio F, et al: Molecular characterization of early human T/NK and B-lymphoid progenitor cells in umbilical cord blood. Blood. 2004, 104 (13): 3918-3926. 10.1182/blood-2004-05-1845.CrossRefPubMed
34.
Lucivero G, Dalla Mora L, Bresciano E, Loria MP, Pezone L, Mancino D: Functional characteristics of cord blood T lymphocytes after lectin and anti-CD3 stimulation. Differences in the way T cells express activation molecules and proliferate. Int J Clin Lab Res. 1996, 26 (4): 255-261. 10.1007/BF02602959.CrossRefPubMed
35.
Nonoyama S, Penix LA, Edwards CP, Lewis DB, Ito S, Aruffo A, Wilson CB, Ochs HD: Diminished expression of CD40 ligand by activated neonatal T cells. J Clin Invest. 1995, 95 (1): 66-75. 10.1172/JCI117677.CrossRefPubMedPubMedCentral
Metadata
Title
T lymphocytes derived from human cord blood provide effective antitumor immunotherapy against a human tumor
Authors
Yong-Soo Lee
Tae-Sik Kim
Dong-Ku Kim
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-225

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