Toward the harmonization of immune monitoring in clinical trials: Quo vadis?
A constantly increasing number of cancer immunotherapies are being investigated in clinical trials but no reliable biomarkers to predict clinical benefit currently exist. For some cancer types, biomarkers have proven to be meaningful predictors of patient outcomes (e.g., BCR-ABL in Chronic Myeloid Leukemia or PSA in prostate cancer) and were established as routine tools. As effects of cancer immunotherapy are mediated through the immune system, immune responses may act as natural biomarkers for clinical efficiency if the right factors can be reliably measured. Following this concept, cancer immunotherapy trials over the last decade have often included measures of tumor-specific cellular immune responses as endpoints to identify reliable surrogates for clinical benefit. Substantial efforts were invested throughout the immunotherapy field in setting up suitable cellular immune assays. However, to date, data from clinical trials do not consistently show that immune responses a ...
- Romero P, Cerottini JC, Speiser DE (2004) Monitoring tumor antigen specific T-cell responses in cancer patients and phase I clinical trials of peptide-based vaccination. Cancer Immunol Immunother 53:249 CrossRef
- Rosenberg SA, Yang JC, Restifo NP (2004) Cancer immunotherapy: moving beyond current vaccines. Nat Med 10:909 CrossRef
- Hoos A, Parmiani G, Hege K, Sznol M, Loibner H, Eggermont A, Urba W, Blumenstein B, Sacks N, Keilholz U, Nichol G (2007) Cancer vaccine clinical trial working groupA clinical development paradigm for cancer vaccines and related biologics. J Immunother 30:1 CrossRef
- Cox JH, Ferrari G, Kalams SA, Lopaczynski W, Oden N, D’Souza MP (2005) Elispot collaborative study group results of an ELISPOT proficiency panel conducted in 11 laboratories participating in international human immunodeficiency virus type 1 vaccine trials. AIDS Res Hum Retroviruses 21:68 CrossRef
- Janetzki S, Cox JH, Oden N, Ferrari G (2005) Standardization and validation issues of the ELISPOT assay. Methods Mol Biol 302:51
- Hanekom WA, Dockrell HM, Ottenhoff THM, Doherty TM, Fletcher H, McShane H, Weichold FF, Hoft DF, Parida SK, Fruth UJ (2007) Immunological outcomes of novel TB vaccine trials: WHO panel recommendations (submitted)
- Speiser DE, Pittet MJ, Guillaume P, Lubenow N, Hoffman E, Cerottini JC, Romero P (2004) Ex vivo analysis of human antigen-specific CD8+ T-cell responses: quality assessment of fluorescent HLA-A2 multimer and interferon-gamma ELISPOT assays for patient immune monitoring. J Immunother 27:298 CrossRef
- Comin-Anduix B, Gualberto A, Glaspy JA, Seja E, Ontiveros M, Reardon DL, Renteria R, Englahner B, Economou JS, Gomez-Navarro J, Ribas A (2006) Definition of an immunologic response using the major histocompatibility complex tetramer and enzyme-linked immunospot assays. Clin Cancer Res 12:107 CrossRef
- Britten CM, Gouttefangeas C, Schoenmaekers-Welters MJP, Pawelec G, Koch S, Ottensmeier C, Mander A, Walter S, Paschen A, Müller-Berghaus J, Haas I, Mackensen A, Køllgaard T, Thor Straten P, Schmitt M, Giannopoulos K, Maier R, Veelken H, Bertinetti C, Konur A, Huber C, Stevanović S, Wölfel T, Van der Burg SH (2007) The CIMT-Monitoring panel: A two-step approach to harmonize the enumeration of antigen-specific CD8+ T lymphocytes by structural and functional assays. Cancer Immunol Immunother. doi:10.1007/s00262-007-0378-0
- Janetzki S, Panageas KS, Ben-Porat L, Boyer J, Britten CM, Clay TM, Kalos M, Maecker HT, Romero P, Yuan J, Kast WA, Hoos A, for the Elispot proficiency panel of the CVC immune assay working group (2007) Results and harmonization guidelines from two large-scale international Elispot proficiency panels conducted by the Cancer Vaccine Consortium (CVC/SVI) Cancer Immunol Immunother. doi:10.1007/s00262-007-0380-6
- Scheibenbogen C, Romero P, Rivoltini L, Herr W, Schmittel A, Cerottini JC, Wölfel T, Eggermont AM, Keilholz U (2000) Quantitation of antigen-reactive T cells in peripheral blood by IFNgamma-ELISPOT assay and chromium-release assay: a four-centre comparative trial. J Immunol Methods 244:81 CrossRef
- Keilholz U, Weber J, Finke JH, Gabrilovich DI, Kast WM, Disis ML, Kirkwood JM, Scheibenbogen C, Schlom J, Maino VC, Lyerly HK, Lee PP, Storkus W, Marincola F, Worobec A, Atkins MB (2002) Immunologic monitoring of cancer vaccine therapy: results of a workshop sponsored by the Society for Biological Therapy. J Immunother 25:97 CrossRef
- Toward the harmonization of immune monitoring in clinical trials: Quo vadis?
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Cancer Immunology, Immunotherapy
Volume 57, Issue 3 , pp 285-288
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- 1. Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
- 2. ZellNet Consulting, Inc., Fort Lee, NJ, USA
- 3. Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
- 4. Department of Immunology, University of Tuebingen, Tuebingen, Germany
- 5. Bristol-Myers Squibb, Wallingford, CT, USA