The defined attenuated Listeria monocytogenes delta mp12 mutant is an effective oral vaccine carrier to trigger a long-lasting immune response against a mouse fibrosarcoma.
Listeria monocytogenes has been proposed as a carrier to elicit major histocompatibility complex class-I restricted immune responses able to protect against tumor challenge. In this study the properties of the attenuated L. monocytogenes delta mp12 mutant has been evaluated in vivo against a highly aggressive mouse fibrosarcoma which expresses beta-galactosidase (beta-gal) as a tumor-associated antigen (TAA). Immunization with the vaccine prototypes resulted in both elicitation of specific antibodies and generation of cytotoxic lymphocytes (CTL). Oral vaccination protected 55-64% of the immunized animals from tumor take (p < 0.01) and strongly reduced the average size of the tumor in the other 34-45% (p < 0.01). Vaccinated mice developed a long-lasting response, which resulted in 100% protection from a subsequent tumor challenge. Substitution of the whole TAA by its CTL-defined immunodominant epitope resulted in 43% protection, suggesting a contribution of the humoral response to the observed antitumor effect. No statistically significant differences were observed in the antitumor response when mice were immunized with strains expressing the immunodominant TAA epitope in the context of carrier proteins which were either exported or restricted to the bacterial cytoplasm. This suggests that the topology of the recombinant antigen does not play a major role in the outcome of the protective response.
Paglia
P
P
Division of Experimental Oncology D, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy. paglia@istitutomori.mi.it
Arioli
I
I
Frahm
N
N
Chakraborty
T
T
Colombo
M P
MP
Guzmàn
C A
CA
D000284:Administration, Oral; D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D001483:Base Sequence; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology*; D007274:Injections, Intraperitoneal; D008089:Listeria monocytogenes / Q000235:genetics* / Q000276:immunology*; D012515:Mast-Cell Sarcoma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D014407:Tumor Cells, Cultured; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics
D000951:Antigens, Neoplasm; D001428:Bacterial Vaccines; D019496:Cancer Vaccines; D002352:Carrier Proteins; D014613:Vaccines, Attenuated