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Surgical Research Reviews| Volume 129, ISSUE 3, P248-254, March 2001

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Direct detection of cellular immune responses to cancer vaccines

      The sub-optimal anti-tumor efficacy of surgery, chemotherapy, and radiotherapy has prompted the search for additional adjunctive therapies, such as immunotherapy. A variety of immunologic strategies for eradicating tumor cells have shown promise in experimental animal models and are being investigated in preclinical studies and clinical trials. A significant challenge is how to establish most reliably and efficiently which of these approaches are clinically effective. Pivotal trials require considerable resources and time—a randomized trial that demonstrated a significant improvement in disease-free survival for patients with colon cancer receiving an autologous vaccine required about 10 years to complete.
      • Vermorken JB
      • Claessen AM
      • van Tinteren H
      • Gall HE
      • Ezinga R
      • Meijer S
      • et al.
      Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial.
      Thus, it is important that intermediate markers of efficacy are explored to help select which of many agents to test for clinical benefit. The traditional developmental strategy for a cytotoxic anti-tumor agent relies on tumor regression as an index of efficacy before initiation of phase III trials, which typically monitor survival as an endpoint. However, the induction of specific immune responses may be the most reliable intermediate marker for immunotherapies, especially in trials conducted in patients with minimal tumor burden.
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      References

        • Vermorken JB
        • Claessen AM
        • van Tinteren H
        • Gall HE
        • Ezinga R
        • Meijer S
        • et al.
        Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial.
        Lancet. 1999; 353: 345-350
        • Lee KH
        • Wang E
        • Nielsen MB
        • Wunderlich J
        • Migueles S
        • Connors M
        • et al.
        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
        • Gajewski TF
        Monitoring specific T-cell responses to melanoma vaccines: ELISPOT, tetramers, and beyond.
        Clin Diag Lab Immunol. 2000; 7: 141-144
        • 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
        • 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
        • Kammula US
        • Lee KH
        • Riker AI
        • Wang E
        • Ohnmacht GA
        • Rosenberg SA
        • et al.
        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
        • Goldberg JE
        • Sherwood SW
        • Clayberger C
        A novel method for measuring CTL and NK cell-mediated cytotoxicity using annexin V and two-color flow cytometry.
        J Immunol Methods. 1999; 224: 1-9
        • van Oers MH
        • Pinkster J
        • Zeijlemaker WP
        Quantification of antigen-reactive cells among human T lymphocytes.
        Eur J Immunol. 1978; 8: 477-484
        • Altman JD
        • Moss PAH
        • Goulder PJR
        • Barouch DH
        • McHeyzer-Williams MG
        • Bell JI
        • et al.
        Phenotypic analysis of antigen-specific T lymphocytes.
        Science. 1996; 274: 94-96
        • Faure F
        • Even J
        • Kourilsky P
        Tumor-specific immune response: current in vitro analyses may not reflect the in vivo immune status.
        Crit Rev Immunol. 1998; 18: 77-86
        • 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
        • McCutcheon M
        • Wehner N
        • Wensky A
        • Kushner M
        • Doan S
        • Hsiao L
        • et al.
        A sensitive ELISPOT assay to detect low-frequency human T lymphocytes.
        J Immunol Methods. 1997; 210: 149-166
        • Asai T
        • Storkus WJ
        • Whiteside TL
        Evaluation of the modified ELISPOT assay for gamma interferon production in cancer patients receiving antitumor vaccines.
        Clin Diag Lab Immunol. 2000; 7: 145-154
        • Tan LC
        • Gudgeon N
        • Annels NE
        • Hansasuta P
        • O'Callaghan CA
        • Rowland-Jones S
        • et al.
        A re-evaluation of the frequency of CD8+ T cells specific for EBV in healthy virus carriers.
        J Immunol. 1999; 162: 1827-1835
        • Callan MF
        • Tan L
        • Annels N
        • Ogg GS
        • Wilson JD
        • O'Callaghan CA
        • et al.
        Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein-Barr virus in vivo.
        J Exp Med. 1998; 187: 1395-1402
        • Lee PP
        • Yee C
        • Savage PA
        • Fong L
        • Brockstedt D
        • Weber JS
        • et al.
        Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients.
        Nat Med. 1999; 5: 677-685
        • Wang XN
        • Proctor SJ
        • Dickinson AM
        Frequency analysis of recipient-reactive helper and cytotoxic T lymphocyte precursors using a combined single limiting dilution assay.
        Transpl Immunol. 1996; 4: 247-251
        • 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