Modulatory effects of mycobacterial heat-shock protein 70 in DNA vaccination against lymphoma.
OBJECTIVE
Pathogen-derived molecules are danger signals and are able to activate innate immunity that in turn controls and regulates generation of adaptive immune responses. Mycobacterium tuberculosis heat shock protein 70 (myc HSP70) has been shown to exert a potent adjuvant effect in vaccination against both infectious agents and solid tumors. Here we explore the use of myc HSP70, as an adjuvant, in DNA vaccination against lymphoma.


METHODS
We describe the effects of vaccination using myc HSP70 encoding plasmid (pHSP70) co-injected with idiotype encoding plasmid (pId), in the 38C13 murine lymphoma model. We dissect mechanisms of anti-tumor immune response and compared efficacy with that of other DNA vaccination strategies.


RESULTS
We show that myc HSP70 plasmid prolongs survival of immunized mice challenged with a high number (2000) of tumor cells. The magnitude of the anti-tumor effect is comparable to that obtained using granulocyte-macrophage colony-stimulating factor (GM-CSF) in the same setting. Moreover, HSP-induced protection is independent from the generation of IgG1 and IgG2a antibodies. Instead, anti-idiotype antibodies of IgG2b subclass develop after vaccination with pHSP as well as with pId and Id-GM-CSF fusion plasmid (pId-GM).


CONCLUSIONS
Co-injection of HSP70 and Id plasmids induces a specific pattern of anti-idiotype immune response able to improve survival of immunized mice.
Liso
Arcangelo
A
Sezione di Ematologia, Università di Foggia, viale Pinto, 71100 Foggia, Italy. a.liso@medicina.unifg.it
Benedetti
Roberta
R
Fagioli
Marta
M
Mariano
Angela
A
Falini
Brunangelo
B
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000917:Antibody Formation; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology / Q000627:therapeutic use*; D008223:Lymphoma / Q000401:mortality / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010957:Plasmids / Q000235:genetics; D016019:Survival Analysis; D014611:Vaccination; D019444:Vaccines, DNA / Q000737:chemistry* / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D018840:HSP70 Heat-Shock Proteins; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor