A MUC1/IL-18 DNA vaccine induces anti-tumor immunity and increased survival in MUC1 transgenic mice.
MUC1 (mucin 1) is a tumor-associated antigen that is overexpressed in many adenocarcinomas. Active immunotherapy targeting tumors expressing MUC1 could have great treatment value. MUC1 DNA vaccines were evaluated in MUC1 transgenic (MUC1.Tg) mice challenged with MC38/MUC1+ tumor cells. Vaccination with MUC1 plasmid DNA (pMUC1) alone was insufficient to induce tumor protection. However, co-administration of pMUC1 with a plasmid encoding murine interleukin-18 (pmuIL-18) resulted in significant tumor protection and survival after tumor challenge. Protection was durable in the absence of additional vaccination, as demonstrated by continued protection of vaccinated mice following tumor rechallenge. Mice surviving challenges with MC38/MUC1+ cells showed significant protection after challenge with MUC1(-) MC38 tumor cells, suggesting that these mice had developed immune responses to epitopes shared between the tumor cell lines. Antibody-mediated depletion of lymphocyte subsets demonstrated that protection was due largely to CD4+ T cells. This work demonstrates that a naked DNA vaccine can break tolerance to MUC1 and induce an immune response capable of mediating both significant protection from tumor challenge and increased survival.
Centocor Inc., 145 King of Prussia Road, Radnor, PA 19087, USA. LSnyder2@CNTUS.JNJ.COM
Linda A
LA
Snyder
Theresa J
TJ
Goletz
George R
GR
Gunn
Frank F
FF
Shi
Michael C
MC
Harris
Karyn
K
Cochlin
Christine
C
McCauley
Stephen G
SG
McCarthy
Patrick J
PJ
Branigan
David M
DM
Knight
D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D005822:Genetic Vectors; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology*; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D018396:Mucin-1; D009077:Mucins / Q000235:genetics / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control*; D010957:Plasmids; D016019:Survival Analysis; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D020382:Interleukin-18; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; D019444:Vaccines, DNA