High-affinity HLA-A(*)02.01 peptides from parathyroid hormone-related protein generate in vitro and in vivo antitumor CTL response without autoimmune side effects

Guido Francini; Antonio Scardino; Kostas Kosmatopoulos; François A Lemonnier; Giuseppe Campoccia; Marianna Sabatino; Daniele Pozzessere; Roberto Petrioli; Luisa Lozzi; Paolo Neri; Giuseppe Fanetti; Maria Grazia Cusi; Pierpaolo Correale

doi:10.4049/jimmunol.169.9.4840

High-affinity HLA-A(*)02.01 peptides from parathyroid hormone-related protein generate in vitro and in vivo antitumor CTL response without autoimmune side effects

J Immunol. 2002 Nov 1;169(9):4840-9. doi: 10.4049/jimmunol.169.9.4840.

Authors

Guido Francini¹, Antonio Scardino, Kostas Kosmatopoulos, François A Lemonnier, Giuseppe Campoccia, Marianna Sabatino, Daniele Pozzessere, Roberto Petrioli, Luisa Lozzi, Paolo Neri, Giuseppe Fanetti, Maria Grazia Cusi, Pierpaolo Correale

Affiliation

¹ Division of Medical Oncology, Institut National de la Santé et de la Recherche Médicale Unité d'Immunité Cellulaire Antivirale, Institut Pasteur, Paris, France. francini@unisi.it

PMID: 12391194
DOI: 10.4049/jimmunol.169.9.4840

Abstract

Parathyroid hormone-related protein (PTH-rP), a protein produced by prostate carcinoma and other epithelial cancers, is a key agent in the development of bone metastases. We investigated whether the protein follows the self-tolerance paradigm or can be used as a target Ag for anticancer immunotherapy by investigating the immunogenicity of two HLA-A(*)02.01-binding PTH-rP-derived peptides (PTR-2 and -4) with different affinity qualities. PTH-rP peptide-specific CTL lines were generated from the PBMC of two HLA-A(*)02.01(+) healthy individuals, stimulated in vitro with PTH-rP peptide-loaded autologous dendritic cells and IL-2. The peptide-specific CTLs were able to kill PTH-rP(+)HLA-A(*)02.01(+) breast and prostate carcinoma cell lines. The two peptides were also able to elicit a strong antitumor PTH-rP-specific CTL response in HLA-A(*)02.01 (HHD) transgenic mice. The vaccinated mice did not show any sign of side effects due to cell-mediated autoimmunity or toxicity. In this study we describe two immunogenic and toxic-free PTH-rP peptides as valid candidates for the design of peptide-based vaccination strategies against prostate cancer and bone metastases from the most common epithelial malignancies.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autoimmunity* / genetics
Binding, Competitive / immunology
Cancer Vaccines / administration & dosage
Cancer Vaccines / adverse effects
Cancer Vaccines / immunology
Cells, Cultured
Cytotoxicity Tests, Immunologic / methods
Cytotoxicity, Immunologic* / genetics
Epitopes, T-Lymphocyte / genetics
Epitopes, T-Lymphocyte / immunology
Female
HLA-A Antigens / genetics
HLA-A Antigens / immunology*
HLA-A Antigens / metabolism
HLA-A2 Antigen / genetics
HLA-A2 Antigen / immunology*
HLA-A2 Antigen / metabolism
Humans
Lymphocyte Activation
Male
Mice
Mice, Transgenic
Neoplasms, Experimental / immunology*
Neoplasms, Experimental / therapy
Oligopeptides / administration & dosage
Oligopeptides / genetics
Oligopeptides / immunology*
Oligopeptides / metabolism
Parathyroid Hormone-Related Protein
Peptide Hormones / administration & dosage
Peptide Hormones / genetics
Peptide Hormones / immunology*
Peptide Hormones / metabolism
Protein Binding / immunology
T-Lymphocytes, Cytotoxic / immunology*
Tumor Cells, Cultured
Vaccines, Synthetic / administration & dosage
Vaccines, Synthetic / adverse effects
Vaccines, Synthetic / immunology

Substances

Cancer Vaccines
Epitopes, T-Lymphocyte
HLA-A Antigens
HLA-A*02:01 antigen
HLA-A2 Antigen
Oligopeptides
PTHLH protein, human
Parathyroid Hormone-Related Protein
Peptide Hormones
Vaccines, Synthetic