Anti-tumor activity of HER-specific peptide vaccines-CKL9 and YL20
(2.Guangzhou Link Health Biotechnology Co., Ltd., Guangzhou, China 510663)
【Abstract】Aim To explore whether the polypeptide vaccines CKL9 and YL20 can induce immune response and anti-tumor effect on HER-2 (+) tumors in vitro and in vivo, and to provide suggestions for clinical use. Methods The proliferation of specific lymphocytes and cytotoxic T lymphocyte activity (CTL) stimulated by CKL9 and YL20 were studied with CCK-8 assay and LDH assay, and the antitumor activity of CKL9 and YL20 was evaluated in vivo. Results The lymphocyte proliferation was promoted by incubation with CKL9 and YL20, and the relative increase of cells was 11.1% and 16.7% respectively at the concentration of 50 mg·L−1 of CKL9 and YL20. The LDH assay confirmed the CTL effect induced by CKL9 and YL20 on HER2-positive tumor cells, not on HER2-negative tumor cells. With an effector–target ratio of 80:1, the inhibition of tumor cell by cytotoxic T-lymphocyte stimulated by CKL9 and YL20 could reach 89.8% and 84.3%, respectively. The HER2 (+) tumor cell N87 transplanted in Babes mice was inhibited by pre-immune polypeptide CKL9 and YL20. Conclusion The HER2-specific polypeptide vaccines CKL9 and YL20 could induce persistent specific CD4 and CD8 T cell immune and inhibit the growth of HER2 positive tumor cells.
【Keywords】 HER-2/neu; peptide vaccination; T-lymphocyte; immune response; N87; anti-tumor activity;
 Zhang X J, Wang W J, Wang J J, et al. Study on anti-tumor effects of polypeptide AP25 [J]. Chin Pharmacol Bull, 2013, 29 (9): 1225–9 (in Chinese).
 Zhang T J, Tian H, Gao X D. Advances in research on antitumor activities of HER2-based peptide vaccines [J]. Prog Pharm Sci, 2013, 37 (10): 516–21 (in Chinese).
 Amin A, Benavides L C, Holmes J P, et al. Assessment of immunologic response and recurrence patterns among patients with clinical recurrence after vaccination with a preventive HER2/neu peptide vaccine:from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02 [J]. Cancer Immunol Immunother, 2008, 57 (12): 1817–25.
 Zhao L J, Li L, Zhou Z Y, et al. A review of the rationale and clinical trials of personalized peptide vaccination [J]. J Mod Oncol, 2014, 22 (3): 676–9 (in Chinese).
 Foy K C, Miller M J, Moldovan N, et al. Combined vaccination with HER-2 peptide followed by therapy with VEGF peptide mimics exerts effective anti-tumor and anti-angiogenic effects in vitro and in vivo [J]. Oncoimmunology, 2012, 1 (7): 1048–60.
 Mohit E, Hashemi A, Allahyari M. Breast cancer immunotherapy: monoclonal antibodies and peptide-based vaccines [J]. Expert Rev Clin Immunol, 2014, 10 (7): 1–35.
 Hueman M T, Stojadinovic A, Storrer C E, et al. Analysis of naive and memory CD4 and CD8 T cell populations in breast cancer patients receiving a HER2/neu peptide (E75) and GM-CSF vaccine [J]. Cancer Immunol Immunother, 2007, 56 (2): 135–46.
 Scott A M, Wolchok J D, Old L J. Antibody therapy of cancer [J]. Nat Rev Cancer, 2012, 12 (4): 278–87.
 Parmiani G, Castelli C, Pilla L, et al. Opposite immune functions of GM-CSF administered as vaccine adjuvant in cancer patients [J]. Ann Oncol, 2007, 18 (2): 226–32.
 Mittendorf E A, Storrer C E, Shriver C D, et al. Investigating the combination of trastuzumab and HER2/neu peptide vaccines for the treatment of breast cancer [J]. Ann Surg Oncol, 2006, 13 (8): 1085–98.
 Hueman M T, Stojadinovic A, Storrer C E, et al. Levels of circulating regulatory CD4+ CD25+ T cells are decreased in breast cancer patients after vaccination with a HER2/neu peptide (E75) and GM-CSF vaccine [J]. Breast Cancer Res Treat, 2006, 98 (1): 17–29.
 Peoples G E, Gurney J M, Hueman M T, et al. Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients [J]. J Clin Oncol, 2005, 23 (30): 7536–45.
 Mittendorf E A, Gurney J M, Storrer C E, et al. Vaccination with a HER2/neu peptide induces intra- and inter-antigenic epitope spreading in patients with early stage breast cancer [J]. Surgery, 2006, 139 (3): 407–18.
 Beignon A S, Brown F, Eftekhari P, et al. A peptide vaccine administered transcutaneously together with cholera toxin elicits potent neutralising anti-FMDV antibody responses [J]. Vet Immunol Immunopathol, 2005, 104 (3–4): 273–80.
 Knutson K L, Schiffman K, Disis M L. Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients [J]. J Clin Invest, 2001, 107 (4): 477–84.
 Patil R, Clifton G T, Holmes J P, et al. Clinical and immunologic responses of HLA-A3+, breast cancer patients vaccinated with the HER2/neu-derived peptide vaccine, E75, in a phase I/II clinical trial [J]. J Am Coll Surg, 2010, 210 (2): 140–7.
 Efferson C L, Schickli J, Ko B K, et al. Activation of tumor antigen-specific cytotoxic T lymphocytes (CTLs) by human dendritic cells infected with an attenuated influenza A virus expressing a CTL epitope derived from the HER-2/neu proto-oncogene [J]. J Virol, 2003, 77 (13): 7411–24.