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

doi:10.3390/cells1020111

. 2012 May 10;1(2):111-26.

doi: 10.3390/cells1020111.

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

Anatoli M Malyguine¹, Susan Strobl², Kimberly Dunham³, Michael R Shurin⁴, Thomas J Sayers⁵

Affiliations

¹ Applied and Developmental Research Support Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. malyguinea@mail.nih.gov.
² Applied and Developmental Research Support Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. stroblsl@mail.nih.gov.
³ Applied and Developmental Research Support Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. dunhamk@mail.nih.gov.
⁴ Departments of Pathology and Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA. shurinmr@upmc.edu.
⁵ Cancer and Inflammation Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. sayerst@mail.nih.gov.

PMID: 24710418
PMCID: PMC3901085
DOI: 10.3390/cells1020111

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

Anatoli M Malyguine et al. Cells. 2012.

. 2012 May 10;1(2):111-26.

doi: 10.3390/cells1020111.

Authors

Anatoli M Malyguine¹, Susan Strobl², Kimberly Dunham³, Michael R Shurin⁴, Thomas J Sayers⁵

Affiliations

¹ Applied and Developmental Research Support Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. malyguinea@mail.nih.gov.
² Applied and Developmental Research Support Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. stroblsl@mail.nih.gov.
³ Applied and Developmental Research Support Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. dunhamk@mail.nih.gov.
⁴ Departments of Pathology and Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA. shurinmr@upmc.edu.
⁵ Cancer and Inflammation Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. sayerst@mail.nih.gov.

PMID: 24710418
PMCID: PMC3901085
DOI: 10.3390/cells1020111

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.

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References

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1. Lee P.P., Yee C., Savage P.A., Fong L., Brockstedt D., Weber J.S., Johnson D., Swetter S., Thompson J., Greenberg P.D., et al. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat. Med. 1999;5:677–685. doi: 10.1038/9525. - DOI - PubMed
1. Monsurro V., Nagorsen D., Wang E., Provenzano M., Dudley M.E., Rosenberg S.A., Marincola F.M. Functional heterogeneity of vaccine-induced CD8(+) T cells. J. Immunol. 2002;168:5933–5942. - PMC - PubMed
1. Scheibenbogen C., Lee K.H., Mayer S., Stevanovic S., Moebius U., Herr W., Rammensee H.G., Keilholz U. A sensitive ELISPOT assay for detection of CD8+ T lymphocytes specific for hla class i-binding peptide epitopes derived from influenza proteins in the blood of healthy donors and melanoma patients. Clin. Cancer Res. 1997;3:221–226. - PubMed
1. Scheibenbogen C., Lee K.H., Stevanovic S., Witzens M., Willhauck M., Waldmann V., Naeher H., Rammensee H.G., Keilholz U. Analysis of the T cell response to tumor and viral peptide antigens by an IFN-gamma- ELISPOT assay. Int. J. Cancer. 1997;71:932–936. doi: 10.1002/(SICI)1097-0215(19970611)71:6<932::AID-IJC3>3.0.CO;2-Z. - DOI - PubMed

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[1] Altman J.D., Moss P.A., Goulder P.J., Barouch D.H., McHeyzer-Williams M.G., Bell J.I., McMichael A.J., Davis M.M. Phenotypic analysis of antigen-specific T lymphocytes. Science. 1996;274:94–96. doi: 10.1126/science.274.5284.94. - DOI - PubMed

[2] Altman J.D., Moss P.A., Goulder P.J., Barouch D.H., McHeyzer-Williams M.G., Bell J.I., McMichael A.J., Davis M.M. Phenotypic analysis of antigen-specific T lymphocytes. Science. 1996;274:94–96. doi: 10.1126/science.274.5284.94. - DOI - PubMed

[3] Lee P.P., Yee C., Savage P.A., Fong L., Brockstedt D., Weber J.S., Johnson D., Swetter S., Thompson J., Greenberg P.D., et al. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat. Med. 1999;5:677–685. doi: 10.1038/9525. - DOI - PubMed

[4] Lee P.P., Yee C., Savage P.A., Fong L., Brockstedt D., Weber J.S., Johnson D., Swetter S., Thompson J., Greenberg P.D., et al. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat. Med. 1999;5:677–685. doi: 10.1038/9525. - DOI - PubMed

[5] Monsurro V., Nagorsen D., Wang E., Provenzano M., Dudley M.E., Rosenberg S.A., Marincola F.M. Functional heterogeneity of vaccine-induced CD8(+) T cells. J. Immunol. 2002;168:5933–5942. - PMC - PubMed

[6] Monsurro V., Nagorsen D., Wang E., Provenzano M., Dudley M.E., Rosenberg S.A., Marincola F.M. Functional heterogeneity of vaccine-induced CD8(+) T cells. J. Immunol. 2002;168:5933–5942. - PMC - PubMed

[7] Scheibenbogen C., Lee K.H., Mayer S., Stevanovic S., Moebius U., Herr W., Rammensee H.G., Keilholz U. A sensitive ELISPOT assay for detection of CD8+ T lymphocytes specific for hla class i-binding peptide epitopes derived from influenza proteins in the blood of healthy donors and melanoma patients. Clin. Cancer Res. 1997;3:221–226. - PubMed

[8] Scheibenbogen C., Lee K.H., Mayer S., Stevanovic S., Moebius U., Herr W., Rammensee H.G., Keilholz U. A sensitive ELISPOT assay for detection of CD8+ T lymphocytes specific for hla class i-binding peptide epitopes derived from influenza proteins in the blood of healthy donors and melanoma patients. Clin. Cancer Res. 1997;3:221–226. - PubMed

[9] Scheibenbogen C., Lee K.H., Stevanovic S., Witzens M., Willhauck M., Waldmann V., Naeher H., Rammensee H.G., Keilholz U. Analysis of the T cell response to tumor and viral peptide antigens by an IFN-gamma- ELISPOT assay. Int. J. Cancer. 1997;71:932–936. doi: 10.1002/(SICI)1097-0215(19970611)71:6<932::AID-IJC3>3.0.CO;2-Z. - DOI - PubMed

[10] Scheibenbogen C., Lee K.H., Stevanovic S., Witzens M., Willhauck M., Waldmann V., Naeher H., Rammensee H.G., Keilholz U. Analysis of the T cell response to tumor and viral peptide antigens by an IFN-gamma- ELISPOT assay. Int. J. Cancer. 1997;71:932–936. doi: 10.1002/(SICI)1097-0215(19970611)71:6<932::AID-IJC3>3.0.CO;2-Z. - DOI - PubMed

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

Affiliations

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

Authors

Affiliations

Abstract

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References

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LinkOut - more resources

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