Analysis of Cellular Immune Responses in Cancer Vaccine Trials

  • Timothy M. Clay
  • Michael A. Morse
  • Paul J. Mosca
  • Amy Hobeika
  • Donna Niedzwiecki
  • H. Kim Lyerly
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Active immunotherapy seeks to stimulate therapeutic immune responses through the use of a wide variety of immunogens. Increasingly, scientific progress in the field has come to rely on the use of assays for detecting and quantifying antigen-specific immune activation and expansion, founded on the belief that these assays may be correlates of in vivo antitumor activity. This is based upon the assumption that induction of an effective antitumor immune response should lead to measurable immune responses. Assays that accurately portray the characteristics of antitumor immune responses would increase our understanding of the effector mechanisms relevant to antitumor activity and help guide the further development of the current vaccines and the next generation of immunotherapeutic strategies. Additionally, accurate immunologic assays could provide intermediate end points for the early evaluation of vaccines and vaccine adjuvants and might provide insight into clinical observations including toxicities and antitumor responses. This perceived link between immunologic assay measurements and antitumor response has not been clearly demonstrated for most current assays of cellular immunologic responses.


Melanoma Patient Cancer Immunotherapy Cancer Vaccine ELISPOT Assay Autologous Tumor Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Tatsumi T, Kierstead LS, Ranieri E, Gesualdo L, Schena FP, Finke JH, Bukowski RM, Mueller-Berghaus J, Kirkwood JM, Kwok WW, Storkus WJ. Disease-associated bias in T helper type 1 (Th1)/Th2 CD4(+) T cell responses against MAGE-6 in HLA-DRB10401(+) patients with renal cell carcinoma or melanoma. J Exp Med 2002; 196:619–628.PubMedCrossRefGoogle Scholar
  2. 2.
    Lauerova L, Dusek L, Simickova M, Kocak I, Vagundova M, Zaloudik J, Kovarik J. Malignant melanoma associates with Thl/Th2 imbalance that coincides with disease progression and immunotherapy response. Neoplasma 2002; 49:159–166.PubMedGoogle Scholar
  3. 3.
    Liew FY. T(H)1 and T(H)2 cells: a historical perspective. Nat Rev Immunol 2002; 2:55–60.PubMedCrossRefGoogle Scholar
  4. 4.
    Simons JW, Mikhak B, Chang JF, DeMarzo AM, Carducci MA, Lim M, et al. Induction of immunity to prostate cancer antigens: results of a clinical trial of vaccination with irradiated autologous prostate tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer. Cancer Res 1999; 59:5160–5168.PubMedGoogle Scholar
  5. 5.
    Puccetti P, Bianchi R, Fioretti MC, Ayroldi E, Uyttenhove C, Van Pel A, Boon T, Grohmann U. Use of a skin test assay to determine tumor-specific CD8+ T cell reactivity. Eur J Immunol 1994; 24:1446–1452.PubMedCrossRefGoogle Scholar
  6. 6.
    Schreiber S, Kampgen E, Wagner E, Pirkhammer D, Trcka J, Korschan H, et al. Immunotherapy of metastatic malignant melanoma by a vaccine consisting of autologous interleukin 2-transfected cancer cells: outcome of a phase I study. Hum Gene Ther 1999; 10:983–993.PubMedCrossRefGoogle Scholar
  7. 7.
    Salgaller ML, Lodge PA, McLean JG, Tjoa BA, Loftus DJ, Ragde H, et al. Report of immune monitoring of prostate cancer patients undergoing T-cell therapy using dendritic cells pulsed with HLA-A2-specific peptides from prostate-specific membrane antigen (PSMA). Prostate 1998; 35:144–151.PubMedCrossRefGoogle Scholar
  8. 8.
    Thurner B, Haendle I, Roder C, Dieckmann D, Keikavoussi P, Jonuleit H, et al. Vaccination with mage3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J Exp Med 1999; 190:1669–1678.PubMedCrossRefGoogle Scholar
  9. 9.
    Morse MA, Deng Y, Coleman D, Hull S, Kitrell-Fisher E, Nair S, Schlom J, Ryback ME, Lyerly HK. A Phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen. Clin Cancer Res 1999; 5:1331–1338.PubMedGoogle Scholar
  10. 10.
    McNeel DG, Schiffman K, Disis ML. Immunization with recombinant human granulocyte-macrophage colony-stimulating factor as a vaccine adjuvant elicits both a cellular and humoral response to recombinant human granulocyte-macrophage colony-stimulating factor. Blood 1999; 93:2653–2659.PubMedGoogle Scholar
  11. 11.
    Tuschong L, Soenen SL, Blaese RM, Candotti F, Muul LM. Immune response to fetal calf serum by two adenosine deaminase-deficient patients after T cell gene therapy. Hum Gene Ther 2002; 13:1605–1610.PubMedCrossRefGoogle Scholar
  12. 12.
    Disis ML, Schiffman K, Gooley TA, McNeel DG, Rinn K, Knutson KL. Delayed-type hypersensitivity response is a predictor of peripheral blood T-cell immunity after HER-2/neu peptide immunization. Clin Cancer Res 2000; 6:1347–1350PubMedGoogle Scholar
  13. 13.
    Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G, Schadendorf D. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med 1998; 4:328–332.PubMedCrossRefGoogle Scholar
  14. 14.
    Waanders GA, Rimoldi D, Lienard D, Carrel S, Lejeune F, Dietrich PY, Cerottini JC, Romero P. Melanoma-reactive human cytotoxic T lymphocytes derived from skin biopsies of delayed-type hypersensitivity reactions induced by injection of an autologous melanoma cell line. Clin Cancer Res 1997; 3:685–696.PubMedGoogle Scholar
  15. 15.
    Lee KH, Wang E, Nielsen MB, Wunderlich J, Migueles S, Connors M, Steinberg SM, Rosenberg SA, Marincola FM. Increased vaccine-specific T cell frequency after peptide-based vaccination correlates with increased susceptibility to in vitro stimulation but does not lead to tumor regression. J Immunol 1999; 163:6292–6300.PubMedGoogle Scholar
  16. 16.
    Panelli MC, Riker A, Kammula U, Wang E, Lee K-H, Rosenberg SA, Marincola FM. Expansion of tumor-T cell pairs from fine needle aspirates of melanoma metastases. J Immunol 2000; 164:495–504.PubMedGoogle Scholar
  17. 17.
    Whiteside TL. Signaling defects in T lymphocytes of patients with malignancy. Cancer Immunol Immunother 1999; 48:346–352.PubMedCrossRefGoogle Scholar
  18. 18.
    Pittet MJ, Valmori D, Dunbar PR, Speiser DE, Lienard D, Lejeune F, Fleischhauer K, Cerundolo V, Cerottini JC, Romero P. High frequencies of naive Melan-A/MART-1-specific CD8(+) T cells in a large proportion of human histocompatibility leukocyte antigen (HLA)-A2 individuals. J Exp Med 1999; 190:705–715.PubMedCrossRefGoogle Scholar
  19. 19.
    Mackensen A, Veelken H, Lahn M, Wittnebel S, Becker D, Kohler G, Kulmburg P, Brennscheidt U, Rosenthal F, Franke B, Mertelsmann R, Lindemann, A. Induction of tumor-specific cytotoxic T lymphocytes by immunization with autologous tumor cells and interleukin-2 gene transfected fibroblasts. J Mol Med 1997; 75:290–296.PubMedCrossRefGoogle Scholar
  20. 20.
    Kalams SA, Johnson RP, Trocha AK, Dynan MJ, Ngo HS, D’ Aquila RT, Kumick JT, Walker BD. Longitudinal analysis of T-cell receptor (TCR) gene usage by human immunodeficiency virus 1 envelope-specific cytotoxic T lymphocyte clones reveals a limited TCR repertoire. J Exp Med 1994; 79:1261–1271.CrossRefGoogle Scholar
  21. 21.
    McKee MD, Clay TM, Rosenberg SA, Nishimura MI. Quantitation of T-cell receptor frequencies by competitive PCR: generation and evaluation of novel TCR subfamily and clone specific competitors. J Immunother 1999; 22:93–102.PubMedCrossRefGoogle Scholar
  22. 22.
    Kourilsky P, Bousso P, Calbo S, Gapin L. Immunological issues in vaccine trials: T-cell responses. Dev Biol Stand 1998; 95:117–124.PubMedGoogle Scholar
  23. 23.
    Argaet VP, Schmidt CW, Burrows SR, Silins SL, Kurilla MG, Doolan DL, Suhrbier A, Moss DJ, Kieff E, Suclley, TB, et al. Dominant selection of an invariant T cell antigen receptor in response to persistent infection by Epstein-Barr virus. J Exp Med 1994; 180:2335–2340.PubMedCrossRefGoogle Scholar
  24. 24.
    Lehner PJ, Wang EC, Moss PA, Williams S, Platt K, Friedman SM, Bell JI, Borysiewicz LK. Human HLA-A0201-restricted cytotoxic T lymphocyte recognition of influenza A is dominated by T cells bearing the V beta 17 gene segment. J Exp Med 1995; 181:79–91.PubMedCrossRefGoogle Scholar
  25. 25.
    Salvi S, Segalla F, Rao S, Arienti F, Sartori M, Bratina G, Caronni E, Anichini A, Clemente C, Parmiani G, Sensi M. Overexpression of the T-cell receptor beta-chain variable region TCRBV14 in HLA-A2matched primary human melanomas. Cancer Res 1995; 55:3374–3379.PubMedGoogle Scholar
  26. 26.
    Sensi M, Salvi S, Castelli C, Maccalli C, Mazzocchi A, Mortarini R, Nicolini G, Herlyn M, Parmiani G, Anichini A. T-cell receptor (TCR) structure of autologous melanoma-reactive cytotoxic T lymphocyte (CTL) clones: tumor-infiltrating lymphocytes overexpress in vivo the TCR beta chain sequence used by an HLA-A2-restricted and melanocyte-lineage-specific CTL clone. J Exp Med 1993; 178:1231–1246.PubMedCrossRefGoogle Scholar
  27. 27.
    Romero P, Gervois N, Schneider J, Escobar P, Valmori D, Pannetier C, Steinle A, Wolfel T, Lienard D, Brichard V, Van Pel A, Jotereau F, Cerottini JC. Cytolytic T lymphocyte recognition of the immunodominant HLA-A*0201-restricted Melan-A/MART-1 antigenic peptide in melanoma. J Immunol 1997; 159:2366–2372.PubMedGoogle Scholar
  28. 28.
    Romero P, Pannetier C, Herman J, Jongeneel CV, Cerottini JC, Coulie PG. Multiple specificities in the repertoire of a melanoma patient’ s cytolytic T lymphocytes directed against tumor antigen MAGE-1 .Al. J Exp Med 1995; 182:1019–1028.PubMedCrossRefGoogle Scholar
  29. 29.
    Weidmann E, Logan TF, Yasumura S, Kirkwood JM, Trucco M, Whiteside TL. Evidence for oligoclonal T-cell response in a metastasis of renal cell carcinoma responding to vaccination with autologous tumor cells and transfer of in vitro-sensitized vaccine-draining lymph node lymphocytes. Cancer Res 1993; 53:4745–4749.PubMedGoogle Scholar
  30. 30.
    Lue C, Mitani Y, Crew MD, George JF, Fink LM, Schichman SA. An automated method for the analysis of T-cell receptor repertoires. Rapid RT-PCR fragment length analysis of the T-cell receptor beta chain complementarity-determining region 3. Am J Clin Pathol 1999; 111:683–690.PubMedGoogle Scholar
  31. 31.
    Altman JD, Moss PAH, Goulder PJR, Barouch DH, McHeyzer-Williams MG, Bell JI, McMichael AJ, Davis MM. Phenotypic analysis of antigen-specific T lymphocytes. Science 1996; 274:94–96.PubMedCrossRefGoogle Scholar
  32. 32.
    Dal Porto J, Johansen TE, Catipovic B, Parfit DJ, Tuveson D, Gether U, Kozlowski S, Fearon DT, Schneck JP. A soluble divalent class I major histocompatibility complex molecule inhibits alloreactive T cells at nanomolar concentrations. Proc Natl Acad Sci USA 1993; 90:6671–6675.CrossRefGoogle Scholar
  33. 33.
    Fahmy T, Bieler J, Schneck J. Probing T cell membrane organization using dimeric MHC-Ig complexes. J Immunol Methods 2002; 268:293.CrossRefGoogle Scholar
  34. 34.
    Yee C, Savage PA, Lee PP, Davis MM, Greenberg PD. Isolation of high avidity melanoma-reactive CTL from heterogeneous populations using peptide-MHC tetramers. J Immunol 1999; 62:2227–2234.Google Scholar
  35. 35.
    Romero P, Dunbar PR, Valmori D, Pittet M, Ogg GS, Rimoldi D, Chen JL, Lienard D, Cerottini JC, Cerundolo V. Ex vivo staining of metastatic lymph nodes by class I major histocompatibility complex tetramers reveals high numbers of antigen-experienced tumor-specific cytolytic T lymphocytes. J Exp Med 1998; 188:1641–1650.PubMedCrossRefGoogle Scholar
  36. 36.
    Dhodapkar MV, Steinman RM, Sapp M, Desai H, Fossella C, Krasovsky J, Donahoe SM, Dunbar PR, Cerundolo V, Nixon DF, Bhardwaj N. Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells. J Clin Invest 1999; 104:173–180.PubMedCrossRefGoogle Scholar
  37. 37.
    Dunbar PR, Ogg GS, Chen J, Rust N, van der Bruggen P, Cerundolo V. Direct isolation, phenotyping and cloning of low-frequency antigen-specific cytotoxic T lymphocytes from peripheral blood. Curr Biol 1998; 8:413–416.PubMedCrossRefGoogle Scholar
  38. 38.
    Khleif SN, Abrams SI, Hamilton JM, Bergmann-Leitner E, Chen A, Bastian A, Bernstein S, Chung Y, Allegra CJ, Schlom J. A phase I vaccine trial with peptides reflecting ras oncogene mutations of solid tumors. J Immunother 1999; 22:155–165.PubMedCrossRefGoogle Scholar
  39. 39.
    Rucker R, Bresler HS, Heffelfinger M, Kim JA, Martin EW Jr, Triozzi PL. Low-dose monoclonal antibody CC49 administered sequentially with granulocyte-macrophage colony-stimulating factor in patients with metastatic colorectal cancer. J Immunother 1999; 22:80–84.PubMedCrossRefGoogle Scholar
  40. 40.
    Sandmaier BM, Oparin DV, Holmberg LA, Reddish MA, MacLean GD, Longenecker BM. Evidence of a cellular immune response against sialyl-Tn in breast and ovarian cancer patients after high-dose chemotherapy, stem cell rescue, immunization with Theratope STn-KLH cancer vaccine. J Immunother 1999; 22:54–66.PubMedCrossRefGoogle Scholar
  41. 41.
    Disis ML, Grabstein KH, Sleath PR, Cheever MA. Generation of immunity to the HER-2/neu oncogenic protein in patients with breast and ovarian cancer using a peptide-based vaccine. Clin Cancer Res 1999; 5:1289–1297.PubMedGoogle Scholar
  42. 42.
    Givan AL, Fisher JL, Waugh M, Ernstoff MS, Wallace PK. A flow cytometric method to estimate the precursor frequencies of cells proliferating in response to specific antigens. J Immunol Methods 1999; 230:99–112.PubMedCrossRefGoogle Scholar
  43. 43.
    Tayebi H, Lienard A, Billot M, Tiberghien P, Herve P, Robinet E. Detection of intracellular cytokines in citrated whole blood or marrow samples by flow cytometry. J Immunol Methods 1999; 229:121–130.PubMedCrossRefGoogle Scholar
  44. 44.
    Vignali DA. Multiplexed particle-based flow cytometric assays. J Immunol Methods 2000; 243: 243–255.PubMedCrossRefGoogle Scholar
  45. 45.
    Czerkinsky C, Andersson G, Ekre HP, Nilsson LA, Klareskog L, Ouchterlony O. Reverse ELISPOT assay for clonal analysis of cytokine production. I. Enumeration of gamma-interferon-secreting cells. J Immunol Methods 1988; 110:29–36.PubMedCrossRefGoogle Scholar
  46. 46.
    Schmittel A, Keilholz U, Scheibenbogen C. Evaluation of the interferon-gamma ELISPOT-assay for quantification of peptide specific T lymphocytes from peripheral blood. J Immunol Methods 1997; 210:167–174.PubMedCrossRefGoogle Scholar
  47. 47.
    Miyahira Y, Murata K, Rodriguez D, Rodriguez JR, Esteban M, Rodrigues MM, Zavala F. Quantification of antigen specific CD8+ T cells using an ELISPOT assay. J Immunol Methods 1995; 181:45–54.PubMedCrossRefGoogle Scholar
  48. 48.
    Enk AH, Wolfel T, Knop J. [Decreased rate of progression and induction of tumor-specific immune response by adjuvant immunotherapy in stage IV melanoma]. Hautarzt 1999; 50:103–108.PubMedCrossRefGoogle Scholar
  49. 49.
    Reynolds SR, Oratz R, Shapiro RL, Hao P, Yun Z, Fotino M, Vukmanovic S, Bystryn JC. Stimulation of CD8+ T-cell responses to MAGE-3 and Melan A/MART-1 by immunization to a polyvalent melanoma vaccine. Int J Cancer 1997; 72:972–976.PubMedCrossRefGoogle Scholar
  50. 50.
    Vaquerano JE, Peng M, Chang JW, Zhou YM, Leong SP. Digital quantification of the enzyme-linked immunospot (ELISPOT). Biotechniques 1998; 25:830–834.PubMedGoogle Scholar
  51. 51.
    Okamoto Y, Abe T, Niwa T, Mizuhashi S, Nishida M. Development of a dual color enzyme-linked immunospot assay for simultaneous detection of murine Thelper type 1- and T helper type 2-cells. Immunopharmacol 1998; 39:107–116.CrossRefGoogle Scholar
  52. 52.
    Slifka MK, Ahmed R. Limiting dilution analysis of virus-specific memory B cells by an ELISPOT assay. J Immunol Methods 1996; 199:37–46.PubMedCrossRefGoogle Scholar
  53. 53.
    Paul WE, Seder RA. Lymphocyte responses and cytokines. Cell 1994; 76:241–251.PubMedCrossRefGoogle Scholar
  54. 54.
    Maino VC, Picker U. Identification of functional subsets by flow cytometry: intracellular detection of cytokine expression. Cytometry 1998; 34:207–215.PubMedCrossRefGoogle Scholar
  55. 55.
    Waldrop SL, Pitcher CJ, Peterson DM, Maino VC, Picker LJ. Determination of antigen-specific memory/ effector CD4+ T cell frequencies by flow cytometry: evidence for a novel, antigen-specific homeostatic mechanism in HIV-associated immunodeficiency. J Clin Invest 1997; 99:1739–1750.PubMedCrossRefGoogle Scholar
  56. 56.
    Suni MA, Picker LJ, Maino VC. Detection of antigen-specific T cell cytokine expression in whole blood by flow cytometry. J Immunol Methods 1998; 212:89–98.PubMedCrossRefGoogle Scholar
  57. 57.
    Maraveyas A, Baban B, Kennard D, Rook GA, Westby M, Grange JM, Lydyard P, Stanford JL, Jones M, Selby P, Dalgleish AG. Possible improved survival of patients with stage IV AJCC melanoma receiving SRL 172 immunotherapy: correlation with induction of increased of intracellular interleukin2 in peripheral blood lymphocytes. Ann Oncol 1999; 10:817–824.PubMedCrossRefGoogle Scholar
  58. 58.
    Reinartz S, Boerner H, Koehler S, Von Ruecker A, Schlebusch H, Wagner U. Evaluation of immunological responses in patients with ovarian cancer treated with the anti-idiotype vaccine ACA125 by determination of intracellular cytokines-a preliminary report. Hybridoma 1999; 18:41–45.PubMedCrossRefGoogle Scholar
  59. 59.
    Heid CA, Stevens J, Livak KJ, Williams PM. Real time quantitative PCR. Genome Res 1996; 6:986–994.PubMedCrossRefGoogle Scholar
  60. 60.
    Kruse N, Pette M, Toyka K, Riekmann P. Quantification of cytokine mRNA expression by RT-PCR in samples of previously frozen blood. J Immunol Methods 1997; 210:195–203.PubMedCrossRefGoogle Scholar
  61. 61.
    Kammula US, Lee K-H, Riker AI, Wang E, Ohnmacht GA, Rosenberg SA, Marincola FM. Functional analysis of antigen-specific T lymphocytes by serial measurement of gene expression in peripheral blood mononuclear cells and tumor specimens. J Immunol 1999; 163:6867–6875.PubMedGoogle Scholar
  62. 62.
    Schwartzentruber DJ, Hom SS, Dadmarz R, White DE, Yannelli JR, Steinberg SM, Rosenberg SA, Topalian SL. In vitro predictors of therapeutic response in melanoma patients receiving tumor-infiltrating lymphocytes and interleukin-2. J Clin Oncol 1994; 12:1475–1483.PubMedGoogle Scholar
  63. 63.
    Marchand M, van Baren N, Weynants P, Brichard V, Dreno B, Tessier MH, Rankin E, Parmiani G, Arienti F, Humblet Y, Bourlond A, Vanwijck R, Lienard D, Beauduin M, Dietrich PY, Russo V, Kerger J, Masucci G, Jager E, De Greve J, Atzpodien J, Brasseur F, Coulie PG, van der Bruggen P, Boon T. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int J Cancer 1999; 80:219–230.PubMedCrossRefGoogle Scholar
  64. 64.
    Tsang KY, Zaremba S, Nieroda CA, Zhu MZ, Hamilton JM, Schlom J. Generation of human cytotoxic T cells specific for human carcinoembryonic antigen epitopes from patients immunized with recombinant vaccinia-CEA vaccine. J Natl Cancer Inst 1995; 87:982–990.PubMedCrossRefGoogle Scholar
  65. 65.
    Dudley ME, Nishimura MI, Holt AK, Rosenberg SA. Antitumor immunization with a minimal peptide epitope (G9–209–2M) leads to a functionally heterogenous CTL response. J Immunother 1999; 22: 288–298.PubMedCrossRefGoogle Scholar
  66. 66.
    van Oers MH, Pinkster J, Zeijlemaker WP. Quantification of antigen-reactive cells among human T lymphocytes. Eur J Immunol 1978; 8:477–484.PubMedCrossRefGoogle Scholar
  67. 67.
    Moller P, Sun Y, Dorbic T, Alijagic S, Makki A, Jurgovsky K, Schroff M, Henz BM, Wittig B, Schadendorf D. Vaccination with IL-7 gene-modified autologous melanoma cells can enhance the antimelanoma lytic activity in peripheral blood of patients with a good clinical performance status: a clinical phase I study. Br J Cancer 1998; 77:1907–1916.PubMedCrossRefGoogle Scholar
  68. 68.
    Sun Y, Jurgovsky K, Moller P, Alijagic S, Dorbic T, Georgieva J, Wittig B, Schadendorf D. Vaccination with IL-12 gene-modified autologous melanoma cells: preclinical results and a first clinical phase I study. Gene Ther 1998; 5:481–490.PubMedCrossRefGoogle Scholar
  69. 69.
    D’ Souza S, Rimoldi D, Lienard D, Lejeune F, Cerottini JC, Romero P. Circulating Melan-A/Mart-1 specific cytolytic T lymphocyte precursors in HLA-A2+ melanoma patients have a memory phenotype. Int J Cancer 1998; 78:699–706.CrossRefGoogle Scholar
  70. 70.
    Romero P, Cerottini JC, Waanders GA. Novel methods to monitor antigen-specific cytotoxic T-cell responses in cancer immunotherapy. Mol Med Today 1998; 4:305–312.PubMedCrossRefGoogle Scholar
  71. 71.
    Tan LC, Gudgeon N, Annels NE, Hansasuta P, O’Callaghan CA, Rowland-Jones S, McMichael AJ, Rickinson AB, Callan MF. A re-evaluation of the frequency of CD8+ T cells specific for EBV in healthy virus carriers. J Immunol 1999; 162:1827–1835.PubMedGoogle Scholar
  72. 72.
    Kuzushima K, Hoshino Y, Fujii K, Yokoyama N, Fujita M, Kiyono T, Kimura H, Morishima T, Morishima Y, Tsurumi T. Rapid determination of Epstein-Barr virus-specific CD8(+) T-cell frequencies by flow cytometry. Blood 1999; 94:3094–3100.PubMedGoogle Scholar
  73. 73.
    Hanson HL, Donermeyer DL, Ikeda H, White JM, Shankaran V, Old LJ, Shiku H, Schreiber RD, Allen PM. Eradication of established tumors by CD8+ T cell adoptive immunotherapy. Immunity 2000; 13:265–276.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2004

Authors and Affiliations

  • Timothy M. Clay
  • Michael A. Morse
  • Paul J. Mosca
  • Amy Hobeika
  • Donna Niedzwiecki
  • H. Kim Lyerly

There are no affiliations available

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