Immunization with a tumor-associated CTL epitope plus a tumor-related or unrelated Th1 helper peptide elicits protective CTL immunity.
Immunization with cytotoxic T cell epitope SPSYVYHQF (AH1), derived from MuLV gp70 envelope protein expressed by CT26 tumor cells, does not protect BALB/c mice against challenge with CT26 tumor cells. By contrast, immunization with AH1 plus T helper peptides OVA(323-337) or SWM(106-118) eliciting Th1 and Th0 profiles, protected 83% and 33% of mice, respectively. Interestingly, immunization with AH1 plus both helper peptides reverted the efficacy to 33%. We identified the endogenous T helper peptide p(320-333) from gp70 which elicits a Th1 profile and is naturally processed. As for OVA(323-337), immunization with p(320-333) alone did not protect against tumor challenge. However, p(320-333) plus AH1 protected 89% of mice at day 10 after vaccination. Only 20% of mice vaccinated with AH1 + OVA(323-337) or AH1 + p(320-333) were protected when challenged 80 days after immunization. Treatment with OVA(323-337) or with p(320-333) around established tumors delayed tumor growth. Our results show that tumor-related as well as tumor-unrelated but strong Th1 peptides may be useful for inducing CTL responses in tumor immunotherapy.
Casares
N
N
Departamento de Medicina Interna, Facultad de Medicina, Universidad de Navarra, Pamplona, Spain.
Lasarte
J J
JJ
de Cerio
A L
AL
Sarobe
P
P
Ruiz
M
M
Melero
I
I
Prieto
J
J
Borrás-Cuesta
F
F
D000276:Adjuvants, Immunologic; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D009211:Myoglobin / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000517:prevention & control; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000276:immunology; D015682:Retroviridae Proteins, Oncogenic / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D013997:Time Factors; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D009211:Myoglobin; D010455:Peptides; D015682:Retroviridae Proteins, Oncogenic; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin