Document Detail


Photoactivated 8-methoxypsoralen treatment causes a peptide-dependent increase in antigen display by transformed lymphocytes.
MedLine Citation:
PMID:  9724096     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ex vivo exposure of malignant human T cells to photoactivated 8-methoxypsoralen (8-MOPa), followed by their i.v. return, appears to vaccinate patients against tumor-associated antigens of cutaneous T cell lymphoma in a procedure termed photopheresis. The molecular basis of this Food and Drug Administration-approved therapy, administered in 100 centers worldwide, is unclear. Most of the attention to the mechanism of action of the drug has focused on its capacity to form covalent cross-links with pyrimidine bases of DNA, thereby inhibiting cellular proliferation. Because immunologic factors appear to be important in the clinical response and could potentially serve as a model for immunotherapy of other malignancies, we explored the possibility that 8-MOP-treated cells display increased quantities of antigenic peptides at their cell surface. In this work, human B-lymphoblastoid tissue culture lines were exposed to 8-MOPa and expression of cell surface class I major histocompatibility complex proteins assessed, since CD8 T cells recognize antigenic moieties in the context of class I molecules. A peak 200-300% increase in MHC class I expression in 8-MOPa-treated cells occurred at 20 hr. 8-MOPa was far more effective in inducing this increase in class I MHC than other modalities, including mitomycin C, gamma-irradiation, ultraviolet B or heat or cold shock. This increase in surface class I MHC molecules appears to be driven by the degradation of cytoplasmic proteins into small peptides, followed by the transport of these peptides to MHC class I molecules in the endoplasmic reticulum. The data suggest that 8-MOPa treatment may augment the immunogenicity of tumor and/or antigen-presenting cells by enhancing processing and transport of class I MHC antigenic peptides.
Authors:
D J Hanlon; C L Berger; R L Edelson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  78     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1998-09-08     Completed Date:  1998-09-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  70-5     Citation Subset:  IM    
Affiliation:
Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520-8059, USA. douglas.hanlon@yale.edu
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD80 / drug effects,  metabolism
B-Lymphocytes / drug effects*,  immunology
Cell Line
Histocompatibility Antigens Class I / drug effects*,  metabolism
Humans
Methoxsalen / pharmacology*
PUVA Therapy
Photosensitizing Agents / pharmacology*
Grant Support
ID/Acronym/Agency:
R01-CA43058/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD80; 0/Histocompatibility Antigens Class I; 0/Photosensitizing Agents; 298-81-7/Methoxsalen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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