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PMID: 24710418 Published · epublish English Journal Article

ELISPOT Assay for Monitoring Cytotoxic T Lymphocytes (CTL) Activity in Cancer Vaccine Clinical Trials.

Cells ·Vol. 1 ·No. 2 ·2012-05-10 ·Pages 111-26

Malyguine AM, Strobl S, Dunham K, Shurin MR, Sayers TJ

Abstract

The profiling and monitoring of immune responses are key elements in the evaluation of the efficacy and development of new biotherapies, and a number of assays have been introduced for analyzing various immune parameters before, during, and after immunotherapy. The choice of immune assays for a given clinical trial depends on the known or suggested immunomodulating mechanisms associated with the tested therapeutic modality. Cell-mediated cytotoxicity represents a key mechanism in the immune response to various pathogens and tumors. Therefore, the selection of monitoring methods for the appropriate assessment of cell-mediated cytotoxicity is thought to be crucial. Assays that can detect both cytotoxic T lymphocytes (CTL) frequency and function, such as the IFN-γ enzyme-linked immunospot assay (ELISPOT) have gained increasing popularity for monitoring clinical trials and in basic research. Results from various clinical trials, including peptide and whole tumor cell vaccination and cytokine treatment, have shown the suitability of the IFN-γ ELISPOT assay for monitoring T cell responses. However, the Granzyme B ELISPOT assay and Perforin ELISPOT assay may represent a more direct analysis of cell-mediated cytotoxicity as compared to the IFN-γ ELISPOT, since Granzyme B and perforin are the key mediators of target cell death via the granule-mediated pathway. In this review we analyze our own data and the data reported by others with regard to the application of various modifications of ELISPOT assays for monitoring CTL activity in clinical vaccine trials.

Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Malyguine Anatoli M
Applied and Developmental Research Support Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. malyguinea@mail.nih.gov.
Strobl Susan
Applied and Developmental Research Support Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. stroblsl@mail.nih.gov.
Dunham Kimberly
Applied and Developmental Research Support Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. dunhamk@mail.nih.gov.
Shurin Michael R
Departments of Pathology and Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA. shurinmr@upmc.edu.
Sayers Thomas J
Cancer and Inflammation Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. sayerst@mail.nih.gov.
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Article Info
Journal
Cells
Abbr.
Cells
ISSN
2073-4409
DOI
10.3390/cells1020111
Email
malyguinea@mail.nih.gov
stroblsl@mail.nih.gov
dunhamk@mail.nih.gov
shurinmr@upmc.edu
sayerst@mail.nih.gov
Published
2012-05-10
Epub
2012-00-10
Pages
111-26
Language
English
Region
Switzerland
NLM ID
101600052
PMCID
PMC3901085
Grants
CCR NIH HHS · HHSN261200800001C · United States
NCI NIH HHS · HHSN261200800001E · United States
External Links
PubMed source DOI: 10.3390/cells1020111 PMC Full Text View journal details
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