CD8+ T-cell-dependent immunity following xenogeneic DNA immunization against CD20 in a tumor challenge model of B-cell lymphoma.
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). IFNgamma 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.
Palomba
Maria Lia
ML
Department of Medicine and Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. palombam@mskcc.org
Roberts
Wendy K
WK
Dao
Tao
T
Manukian
Gregory
G
Guevara-Patiño
Jose A
JA
Wolchok
Jedd D
JD
Scheinberg
David A
DA
Houghton
Alan N
AN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D018951:Antigens, CD20 / Q000096:biosynthesis* / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology; D019470:Biolistics; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018076:DNA, Complementary / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007313:Insecta; D007371:Interferon-gamma / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000628:therapy*; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D013997:Time Factors; D019444:Vaccines, DNA
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D000939:Epitopes; D010455:Peptides; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D007371:Interferon-gamma