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:	http://www.scopus.com/inward/record.url?eid=2-s2.0-11144353596&partnerID=40&md5=c193dd99e04f4f3f813ec5f2aa71b604
Notes:	Vaccine -- Cited By (since 1996):77 -- Export Date: 16 June 2014 -- CODEN: VACCD -- Source: Scopus