Towards new immunotherapies: targeting recombinant cytokines to the immune system using live attenuated Salmonella.
We have used Salmonella as a delivery system for eukaryotic expression plasmids encoding cytokines, and assessed its capacity to modulate immune responses in different experimental models. Plasmids encoding mouse IL-4 and IL-18 under cytomegalovirus promoter were constructed and transformed into live attenuated Salmonella enterica serovar Typhi strain CVD 908-htrA, and Salmonella enterica serovar Typhimurium strain SL3261. We have shown that systemic as well as mucosal immunization with such constructs can influence the antibody and cytokine responses to the Salmonella carrier and to co-administered bystander antigens, as well as the specific immune response elicited during a parasitic infection. Further, we have shown that oral cytokine-therapy using Salmonella as gene vector induce antitumoral effect as demonstrated by extended survival time in melanoma-bearing mice. This approach may be particularly suited for the development of new immunotherapies with applications in parasitic infections and cancer, were alterations of the host's immune responses are usually found, and therapy-induced modulation of the immune response is likely to be required.
Rosenkranz
Claudia D
CD
Department of Biotechnology, Instituto de Higiene, Facultad de Medicina, Avda A. Navarro 3051, Montevideo, CP 11200, Uruguay.
Chiara
Damasia
D
Agorio
Caroline
C
Baz
Adriana
A
Pasetti
Marcela F
MF
Schreiber
Fernanda
F
Dematteis
Silvia
S
Martinez
Miguel
M
Sztein
Marcelo B
MB
Chabalgoity
Jose A
JA
D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D016207:Cytokines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016503:Drug Delivery Systems; D004443:Echinococcosis / Q000276:immunology / Q000628:therapy; D015316:Genetic Therapy; D005822:Genetic Vectors; D007167:Immunotherapy; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D051379:Mice; D010957:Plasmids; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012485:Salmonella typhi / Q000235:genetics / Q000378:metabolism*; D014613:Vaccines, Attenuated / Q000276:immunology
D016207:Cytokines; D011994:Recombinant Proteins; D014613:Vaccines, Attenuated