Focussed Research Review

Cancer Immunology, Immunotherapy

, 58:789

First online:

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

  • Ann ManderAffiliated withCancer Sciences Division, School of Medicine, Southampton General Hospital, University of Southampton Email author 
  • , Ferdousi ChowdhuryAffiliated withCancer Sciences Division, School of Medicine, Southampton General Hospital, University of Southampton
  • , Lindsey LowAffiliated withCancer Sciences Division, School of Medicine, Southampton General Hospital, University of Southampton
  • , Christian H. OttensmeierAffiliated withCancer Sciences Division, School of Medicine, Southampton General Hospital, University of Southampton

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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 IFNγ ELISPOTs to assess humoral and cellular responses to the vaccines over time. The validated primary endpoint assay, a peptide-specific CD8+ IFNγ 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.

Keywords

Immunotherapy Immunomonitoring Assay validation DNA fusion vaccine CEA PSMA