Immunization with a tumor‐associated CTL epitope plus a tumor‐related or unrelated Th1 helper peptide elicits protective CTL immunity

• Published in: European journal of immunology 2001-06, Vol.31 (6), p.1780-1789
• Main Authors: Casares, Noelia, Lasarte, Juan José, Cerio, Ascensión López‐Díaz de, Sarobe, Pablo, Ruiz, Marta, Melero, Ignacio, Prieto, Jesús, Borrás‐Cuesta, Francisco
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic; Animals; Cancer Vaccines - immunology; CTL; Cytokine; Epitopes, T-Lymphocyte - immunology; Female; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Interleukin-4 - biosynthesis; Lung Neoplasms - prevention & control; Lung Neoplasms - secondary; Mice; Mice, Inbred BALB C; Myoglobin - immunology; Neoplasms - immunology; Neoplasms - prevention & control; Ovalbumin - immunology; Peptides - immunology; Retroviridae Proteins, Oncogenic - immunology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Helper-Inducer - immunology; Th1 Cells - immunology; Th1/Th2; Time Factors; Tumor immunity; Vaccination; Vaccines, Synthetic - immunology; Viral Envelope Proteins - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/1521-4141(200106)31:6<1780::AID-IMMU1780>3.0.CO;2-I

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.