CD8+ T-cell-dependent immunity following xenogeneic DNA immunization against CD20 in a tumor challenge model of B-cell lymphoma Journal Article

Authors: Palomba, M. L.; Roberts, W. K.; Dao, T.; Manukian, G.; Guevara-Patiño, J. A.; Wolchok, J. D.; Scheinberg, D. A.; Houghton, A. N.
Article Title: CD8+ T-cell-dependent immunity following xenogeneic DNA immunization against CD20 in a tumor challenge model of B-cell lymphoma
Abstract: The CD20 B-cell differentiation antigen is an attractive target for immunotherapy of B-cell lymphomas. In an experimental lymphoma model, BALB/c mice were immunized with mouse or human CD20 cDNA (mCD20 and hCD20, respectively) or their extracellular domains (minigenes). IFNγ secretion by CD8+ T cells against CD20 was detected in mice vaccinated with hCD20 or human minigene, indicating that hCD20-primed CD8+ T cells recognize syngeneic CD20. Systemic challenge with syngeneic A20 cells, an aggressive lymphoma, resulted in long-term survival in a subset of immunized mice. Overall long-term survival was 14% in groups vaccinated with the human minigene versus 4% in control groups (P < 0.001). CD8+ T-cell depletion during the effector phase completely abrogated this effect. Antibodies against a recombinant mouse CD20 protein produced in insect cells were detected in mice immunized with hCD20 DNA and human and mouse minigene, but not in mice receiving mCD20 DNA. These results show that active immunization with xenogeneic DNA vaccines can induce CD8+ T cell-dependent immunity against CD20.
Keywords: cancer survival; controlled study; nonhuman; neoplasms; t lymphocyte; cd8-positive t-lymphocytes; animal cell; mouse; animals; mice; animal tissue; animal experiment; animal model; antineoplastic activity; in vitro study; mice, inbred balb c; time factors; b cell lymphoma; blotting, western; lymphoma, b-cell; cd20 antigen; antigens, cd20; antibodies, monoclonal; cellular immunity; immunotherapy; antigens, neoplasm; recombinant fusion proteins; gamma interferon; antibody response; cd4-positive t-lymphocytes; recombinant proteins; recombinant protein; peptides; plasmids; dna vaccine; protein structure, tertiary; neoplasm transplantation; mouse strain; enzyme-linked immunosorbent assay; cytokine release; tumor rejection; vaccines, dna; dna, complementary; major histocompatibility antigen class 1; epitopes; insects; biolistics; insect cell; active immunization; interferon type ii
Journal Title: Clinical Cancer Research
Volume: 11
Issue: 1
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2005-01-01
Start Page: 370
End Page: 379
Language: English
PUBMED: 15671568
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 19" - "Export Date: 24 October 2012" - "CODEN: CCREF" - "Source: Scopus"