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PMID: 8666894 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Therapy of murine tumors with p53 wild-type and mutant sequence peptide-based vaccines.

The Journal of experimental medicine ·Vol. 183 ·No. 4 ·1996-04-01 ·Pages 1357-65

Mayordomo JI, Loftus DJ, Sakamoto H, De Cesare CM, Appasamy PM, Lotze MT, Storkus WJ, Appella E, DeLeo AB

Abstract

The BALB/c Meth A sarcoma carries a p53 missense mutation at codon 234, which occurs in a peptide, termed 234CM, capable of being presented to cytotoxic T lymphocytes (CTL) by H-2Kd molecules (Noguchi, Y., E.C. Richards, Y.-T. Chen, and L.J. Old. 1994. Proc. Natl. Acad. Sci. USA. 91:3171-3175). Immunization of BALB/c mice with bone marrow-derived dendritic cells (DC), generated in the presence of granulocyte macrophage colony-stimulating factor and interleukin 4, and prepulsed with the Meth A p53 mutant peptide, induced CTL that specifically recognized peptide-pulsed P815 cells, as well as Meth A cells naturally expressing this epitope. Immunization with this vaccine also protected naive mice from a subsequent tumor challenge, and it inhibited tumor growth in mice bearing day 7 subcutaneous Meth A tumors. We additionally determined that immunization of BALB/c mice with DC pulsed with the p53 peptide containing the wild-type residue at position 234, 234CW, induced peptide-specific CTL that reacted against several methylcholanthrene-induced BALB/c sarcomas, including CMS4 sarcoma, and rejection of CMS4 sarcoma in vaccination and therapy (day 7) protocols. These results support the efficacy of DC-based, p53-derived peptide vaccines for the immunotherapy of cancer. The translational potential of this strategy is enhanced by previous reports showing that DC can readily be generated from human peripheral blood lymphocytes.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Cytotoxicity, Immunologic Dendritic Cells/immunology Histocompatibility Antigens Class I/metabolism Molecular Sequence Data Peptide Fragments/genetics,immunology,metabolism,therapeutic use Protein Binding Sarcoma, Experimental/therapy Tumor Suppressor Protein p53/genetics,immunology,metabolism,therapeutic use Vaccination
Chemicals
Histocompatibility Antigens Class I Peptide Fragments Tumor Suppressor Protein p53
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Mayordomo J I
Department of Genetics and Biochemistry, School of Medicine, University of Pittsburgh, Pennsylvania 15213-2582, USA.
Loftus D J
Sakamoto H
De Cesare C M
Appasamy P M
Lotze M T
Storkus W J
Appella E
DeLeo A B
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.183.4.1357
Published
1996-04-01
Pages
1357-65
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192493
Subset
IM
Grants
NIAID NIH HHS · AI 31515 · United States
NCI NIH HHS · CA 57840 · United States
External Links
PubMed source DOI: 10.1084/jem.183.4.1357 PMC Full Text View journal details
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