1. Fit for purpose? A case study: validation of immunological endpoint assays for the detection of cellular and humoral responses to anti-tumour DNA fusion vaccines.
- Author
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Mander A, Chowdhury F, Low L, and Ottensmeier CH
- Subjects
- Adenocarcinoma immunology, Adenocarcinoma therapy, Animals, Antibodies, Neoplasm biosynthesis, Antibodies, Neoplasm immunology, Follow-Up Studies, Humans, Immunity, Cellular, Male, Mice, Neoplasms immunology, Peptide Fragments genetics, Prostate-Specific Antigen genetics, Prostatic Neoplasms immunology, Prostatic Neoplasms therapy, Recombinant Fusion Proteins immunology, T-Lymphocytes metabolism, Tetanus Toxin genetics, United Kingdom, Antibodies, Neoplasm blood, Antigens, Neoplasm immunology, Cancer Vaccines immunology, Carcinoembryonic Antigen immunology, Clinical Trials, Phase II as Topic standards, Enzyme-Linked Immunosorbent Assay, HLA-A2 Antigen immunology, Interferon-gamma blood, Multicenter Studies as Topic standards, Neoplasms therapy, Peptide Fragments immunology, Prostate-Specific Antigen immunology, Tetanus Toxin immunology, Vaccines, DNA immunology
- Abstract
Clinical trials are governed by an increasingly stringent regulatory framework, which applies to all levels of trial conduct. Study critical immunological endpoints, which define success or failure in early phase clinical immunological trials, require formal pre-trial validation. In this case study, we describe the assay validation process, during which the sensitivity, and precision of immunological endpoint assays were defined. The purpose was the evaluation of two multicentre phase I/II clinical trials from our unit in Southampton, UK, which assess the effects of DNA fusion vaccines on immune responses in HLA-A2+ patients with carcinoembryonic antigen (CEA)-expressing malignancies and prostate cancer. Validated immunomonitoring is being performed using ELISA and IFNgamma ELISPOTs to assess humoral and cellular responses to the vaccines over time. The validated primary endpoint assay, a peptide-specific CD8+ IFNgamma ELISPOT, was tested in a pre-trial study and found to be suitable for the detection of low frequency naturally occurring CEA- and prostate-derived tumour-antigen-specific T cells in patients with CEA-expressing malignancies and prostate cancer.
- Published
- 2009
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