CTLA-4 blockade in combination with xenogeneic DNA vaccines enhances T-cell responses, tumor immunity and autoimmunity to self antigens in animal and cellular model systems Journal Article


Authors: Gregor, P. D.; Wolchok, J. D.; Ferrone, C. R.; Buchinsky, H.; Guevara-Patiño, J. A.; Perales, M. A.; Mortazavi, F.; Bacich, D.; Heston, W.; Latouche, J. B.; Sadelain, M.; Allison, J. P.; Scher, H. I.; Houghton, A. N.
Article Title: CTLA-4 blockade in combination with xenogeneic DNA vaccines enhances T-cell responses, tumor immunity and autoimmunity to self antigens in animal and cellular model systems
Abstract: Xenogeneic DNA vaccination can elicit tumor immunity through T cell and antibody-dependent effector mechanisms. Blockade of CTLA-4 engagement with B7 expressed on APCs has been shown to enhance T cell-dependent immunity. We investigated whether CTLA-4 blockade could increase T-cell responses and tumor immunity elicited by DNA vaccines. CTLA-4 blockade enhanced B16 tumor rejection in mice immunized against the melanoma differentiation antigens tyrosinase-related protein 2 and gp100, and this effect was stronger when anti-CTLA-4 was administered with booster vaccinations. CTLA-4 blockade also increased the T-cell responses to prostate-specific membrane antigen (PSMA) when given with the second or third vaccination. Based on these pre-clinical studies, we suggest that anti-CTLA-4 should be tested with xenogeneic DNA vaccines against cancer and that special attention should be given to sequence and schedule of administration. © 2004 Elsevier Ltd. All rights reserved.
Keywords: controlled study; nonhuman; flow cytometry; neoplasms; t-lymphocytes; animal cell; mouse; animals; mice; glycoprotein gp 100; animal experiment; animal model; cell line, tumor; mice, inbred balb c; mice, inbred c57bl; prostate specific membrane antigen; prostate; cellular immunity; cancer vaccines; melanoma b16; melanoma, experimental; autoantigen; autoantigens; tumor immunity; plasmids; inhibition kinetics; autoimmunity; dna vaccine; ctla-4; antigens, cd; neoplasm transplantation; cytotoxic t lymphocyte antigen 4; tumor rejection; vaccines, dna; antibodies, neoplasm; immunosuppressive agents; antigens, differentiation; immunization; immunity, cellular; tyrosinase related protein 2; process model; immunization schedule; cancer; humans; male; female; priority journal; article
Journal Title: Vaccine
Volume: 22
Issue: 13-14
ISSN: 0264-410X
Publisher: Elsevier Inc.  
Date Published: 2004-04-16
Start Page: 1700
End Page: 1708
Language: English
DOI: 10.1016/j.vaccine.2003.10.048
PROVIDER: scopus
PUBMED: 15068853
DOI/URL:
Notes: Vaccine -- Cited By (since 1996):77 -- Export Date: 16 June 2014 -- CODEN: VACCD -- Source: Scopus
Altmetric
Citation Impact
MSK Authors
  1. Cristina Ferrone
    32 Ferrone
  2. Polly Gregor
    29 Gregor
  3. Jedd D Wolchok
    815 Wolchok
  4. Miguel-Angel Perales
    588 Perales
  5. Michel W J Sadelain
    514 Sadelain
  6. Howard Scher
    1049 Scher
  7. Alan N Houghton
    336 Houghton