Peptide vaccination of patients with metastatic melanoma: Improved clinical outcome in patients demonstrating effective immunization

Svetomir N. Markovic, Vera J. Suman, James N. Ingle, Judith S. Kaur, Henry C. Pitot, Charles L. Loprinzi, Ravi D. Rao, Edward T. Creagan, Mark R. Pittelkow, Jakob B. Allred, Wendy K. Nevala, Esteban Celis

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

OBJECTIVES: Therapeutic peptide vaccines for melanoma continue to only demonstrate anecdotal success. We set out to evaluate the impact of low-dose GM-CSF emulsified in Montanide ISA-51 on the immunogenicity of HLA-A2 restricted melanoma differentiation antigen peptide vaccines (MART-1, gp100 and tyrosinase) administered in separate subcutaneous injections. METHODS: We conducted a randomized phase II clinical trial of HLA-A2+ patients with metastatic melanoma that were immunized every 3 weeks with one of the following vaccine preparations: (A) peptides + Montanide ISA-51; (B) peptides + Montanide ISA-51 + GM-CSF (10 μg); (C) peptides + Montanide ISA-51 + GM-CSF (50 μg). Immunization efficacy was determined by quantification of vaccine specific tetramer positive cytotoxic T cells in peripheral blood. Global assessment of immune competence was ascertained using DTH testing to common recall antigens as well as peripheral blood immunophenotyping. RESULTS: Twenty-five eligible patients were equally distributed across all 3 treatment groups. Only 9 patients demonstrated evidence of immunization. Most commonly, immune response was achieved to the gp100 peptide. The addition of low-dose GM-CSF did not impact immunization efficacy. DTH reactivity to Candida appeared predictive of successful immunization. Successful immunization with the peptide vaccines was associated with improved clinical outcomes. CONCLUSIONS: The addition of low dose GM-CSF to peptide vaccines did not enhance immunogenicity. Higher doses of GM-CSF may be needed to achieve this effect and this is a testable hypothesis. Likewise, better patient selection based on immunologic status (DTH reactivity) may be helpful to better understand the clinical impact of therapeutic cancer vaccines.

Original languageEnglish (US)
Pages (from-to)352-360
Number of pages9
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume29
Issue number4
DOIs
StatePublished - Aug 1 2006

Fingerprint

Granulocyte-Macrophage Colony-Stimulating Factor
Melanoma
Immunization
Vaccination
Subunit Vaccines
Peptides
HLA-A2 Antigen
Vaccines
Melanoma-Specific Antigens
Immunophenotyping
Phase II Clinical Trials
Cancer Vaccines
Monophenol Monooxygenase
C-Peptide
Differentiation Antigens
Subcutaneous Injections
Candida
Mental Competency
Patient Selection
Therapeutics

Keywords

  • GM-CSF
  • Melanoma
  • Metastatic
  • Peptides
  • T cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Peptide vaccination of patients with metastatic melanoma : Improved clinical outcome in patients demonstrating effective immunization. / Markovic, Svetomir N.; Suman, Vera J.; Ingle, James N.; Kaur, Judith S.; Pitot, Henry C.; Loprinzi, Charles L.; Rao, Ravi D.; Creagan, Edward T.; Pittelkow, Mark R.; Allred, Jakob B.; Nevala, Wendy K.; Celis, Esteban.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 29, No. 4, 01.08.2006, p. 352-360.

Research output: Contribution to journalArticle

Markovic, SN, Suman, VJ, Ingle, JN, Kaur, JS, Pitot, HC, Loprinzi, CL, Rao, RD, Creagan, ET, Pittelkow, MR, Allred, JB, Nevala, WK & Celis, E 2006, 'Peptide vaccination of patients with metastatic melanoma: Improved clinical outcome in patients demonstrating effective immunization', American Journal of Clinical Oncology: Cancer Clinical Trials, vol. 29, no. 4, pp. 352-360. https://doi.org/10.1097/01.coc.0000217877.78473.a4
Markovic, Svetomir N. ; Suman, Vera J. ; Ingle, James N. ; Kaur, Judith S. ; Pitot, Henry C. ; Loprinzi, Charles L. ; Rao, Ravi D. ; Creagan, Edward T. ; Pittelkow, Mark R. ; Allred, Jakob B. ; Nevala, Wendy K. ; Celis, Esteban. / Peptide vaccination of patients with metastatic melanoma : Improved clinical outcome in patients demonstrating effective immunization. In: American Journal of Clinical Oncology: Cancer Clinical Trials. 2006 ; Vol. 29, No. 4. pp. 352-360.
@article{8e5edcb10de94be38a0e1eddc3cad98a,
title = "Peptide vaccination of patients with metastatic melanoma: Improved clinical outcome in patients demonstrating effective immunization",
abstract = "OBJECTIVES: Therapeutic peptide vaccines for melanoma continue to only demonstrate anecdotal success. We set out to evaluate the impact of low-dose GM-CSF emulsified in Montanide ISA-51 on the immunogenicity of HLA-A2 restricted melanoma differentiation antigen peptide vaccines (MART-1, gp100 and tyrosinase) administered in separate subcutaneous injections. METHODS: We conducted a randomized phase II clinical trial of HLA-A2+ patients with metastatic melanoma that were immunized every 3 weeks with one of the following vaccine preparations: (A) peptides + Montanide ISA-51; (B) peptides + Montanide ISA-51 + GM-CSF (10 μg); (C) peptides + Montanide ISA-51 + GM-CSF (50 μg). Immunization efficacy was determined by quantification of vaccine specific tetramer positive cytotoxic T cells in peripheral blood. Global assessment of immune competence was ascertained using DTH testing to common recall antigens as well as peripheral blood immunophenotyping. RESULTS: Twenty-five eligible patients were equally distributed across all 3 treatment groups. Only 9 patients demonstrated evidence of immunization. Most commonly, immune response was achieved to the gp100 peptide. The addition of low-dose GM-CSF did not impact immunization efficacy. DTH reactivity to Candida appeared predictive of successful immunization. Successful immunization with the peptide vaccines was associated with improved clinical outcomes. CONCLUSIONS: The addition of low dose GM-CSF to peptide vaccines did not enhance immunogenicity. Higher doses of GM-CSF may be needed to achieve this effect and this is a testable hypothesis. Likewise, better patient selection based on immunologic status (DTH reactivity) may be helpful to better understand the clinical impact of therapeutic cancer vaccines.",
keywords = "GM-CSF, Melanoma, Metastatic, Peptides, T cells",
author = "Markovic, {Svetomir N.} and Suman, {Vera J.} and Ingle, {James N.} and Kaur, {Judith S.} and Pitot, {Henry C.} and Loprinzi, {Charles L.} and Rao, {Ravi D.} and Creagan, {Edward T.} and Pittelkow, {Mark R.} and Allred, {Jakob B.} and Nevala, {Wendy K.} and Esteban Celis",
year = "2006",
month = "8",
day = "1",
doi = "10.1097/01.coc.0000217877.78473.a4",
language = "English (US)",
volume = "29",
pages = "352--360",
journal = "American Journal of Clinical Oncology",
issn = "0277-3732",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Peptide vaccination of patients with metastatic melanoma

T2 - Improved clinical outcome in patients demonstrating effective immunization

AU - Markovic, Svetomir N.

AU - Suman, Vera J.

AU - Ingle, James N.

AU - Kaur, Judith S.

AU - Pitot, Henry C.

AU - Loprinzi, Charles L.

AU - Rao, Ravi D.

AU - Creagan, Edward T.

AU - Pittelkow, Mark R.

AU - Allred, Jakob B.

AU - Nevala, Wendy K.

AU - Celis, Esteban

PY - 2006/8/1

Y1 - 2006/8/1

N2 - OBJECTIVES: Therapeutic peptide vaccines for melanoma continue to only demonstrate anecdotal success. We set out to evaluate the impact of low-dose GM-CSF emulsified in Montanide ISA-51 on the immunogenicity of HLA-A2 restricted melanoma differentiation antigen peptide vaccines (MART-1, gp100 and tyrosinase) administered in separate subcutaneous injections. METHODS: We conducted a randomized phase II clinical trial of HLA-A2+ patients with metastatic melanoma that were immunized every 3 weeks with one of the following vaccine preparations: (A) peptides + Montanide ISA-51; (B) peptides + Montanide ISA-51 + GM-CSF (10 μg); (C) peptides + Montanide ISA-51 + GM-CSF (50 μg). Immunization efficacy was determined by quantification of vaccine specific tetramer positive cytotoxic T cells in peripheral blood. Global assessment of immune competence was ascertained using DTH testing to common recall antigens as well as peripheral blood immunophenotyping. RESULTS: Twenty-five eligible patients were equally distributed across all 3 treatment groups. Only 9 patients demonstrated evidence of immunization. Most commonly, immune response was achieved to the gp100 peptide. The addition of low-dose GM-CSF did not impact immunization efficacy. DTH reactivity to Candida appeared predictive of successful immunization. Successful immunization with the peptide vaccines was associated with improved clinical outcomes. CONCLUSIONS: The addition of low dose GM-CSF to peptide vaccines did not enhance immunogenicity. Higher doses of GM-CSF may be needed to achieve this effect and this is a testable hypothesis. Likewise, better patient selection based on immunologic status (DTH reactivity) may be helpful to better understand the clinical impact of therapeutic cancer vaccines.

AB - OBJECTIVES: Therapeutic peptide vaccines for melanoma continue to only demonstrate anecdotal success. We set out to evaluate the impact of low-dose GM-CSF emulsified in Montanide ISA-51 on the immunogenicity of HLA-A2 restricted melanoma differentiation antigen peptide vaccines (MART-1, gp100 and tyrosinase) administered in separate subcutaneous injections. METHODS: We conducted a randomized phase II clinical trial of HLA-A2+ patients with metastatic melanoma that were immunized every 3 weeks with one of the following vaccine preparations: (A) peptides + Montanide ISA-51; (B) peptides + Montanide ISA-51 + GM-CSF (10 μg); (C) peptides + Montanide ISA-51 + GM-CSF (50 μg). Immunization efficacy was determined by quantification of vaccine specific tetramer positive cytotoxic T cells in peripheral blood. Global assessment of immune competence was ascertained using DTH testing to common recall antigens as well as peripheral blood immunophenotyping. RESULTS: Twenty-five eligible patients were equally distributed across all 3 treatment groups. Only 9 patients demonstrated evidence of immunization. Most commonly, immune response was achieved to the gp100 peptide. The addition of low-dose GM-CSF did not impact immunization efficacy. DTH reactivity to Candida appeared predictive of successful immunization. Successful immunization with the peptide vaccines was associated with improved clinical outcomes. CONCLUSIONS: The addition of low dose GM-CSF to peptide vaccines did not enhance immunogenicity. Higher doses of GM-CSF may be needed to achieve this effect and this is a testable hypothesis. Likewise, better patient selection based on immunologic status (DTH reactivity) may be helpful to better understand the clinical impact of therapeutic cancer vaccines.

KW - GM-CSF

KW - Melanoma

KW - Metastatic

KW - Peptides

KW - T cells

UR - http://www.scopus.com/inward/record.url?scp=33746802910&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746802910&partnerID=8YFLogxK

U2 - 10.1097/01.coc.0000217877.78473.a4

DO - 10.1097/01.coc.0000217877.78473.a4

M3 - Article

C2 - 16891861

AN - SCOPUS:33746802910

VL - 29

SP - 352

EP - 360

JO - American Journal of Clinical Oncology

JF - American Journal of Clinical Oncology

SN - 0277-3732

IS - 4

ER -