Dual anti-tumor polypeptide based on Eps8-EGFR binding domain

An eps8-egfr, anti-tumor technology, applied in the field of preparing anti-tumor drugs, can solve the problems of unsatisfactory tumor cell proliferation inhibition effect and low inhibition rate, etc.

Inactive Publication Date: 2016-08-17
SOUTHERN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, follow-up studies by the inventors found that the inhibitory effect of the above-mentioned CTL epitope peptides on tumor cell proliferation was not ideal, and the inhibition rates were all lower than 50%.

Method used

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  • Dual anti-tumor polypeptide based on Eps8-EGFR binding domain
  • Dual anti-tumor polypeptide based on Eps8-EGFR binding domain
  • Dual anti-tumor polypeptide based on Eps8-EGFR binding domain

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Embodiment 1 (screening of Eps8-EGFR binding domain polypeptide)

[0024] The anti-tumor polypeptide derived from the Eps8-EGFR domain of the present invention is based on the primary structure of the antigen, using immunoinformatics means, and using the online biological software SYFPEITHI (http: / / www.syfpeithi.de / bin / MHCServer .dll / EpitopePrediction.htm) (the algorithm is described in Rammensee H, et al. Immunogenetics 1999; 50(3-4):213-219.) and BIMAS (http: / / www-bimas.cit.nih.gov / molbio / hla_bind / ) (this algorithm is described in Parker KC, et al. J Immunol 1994; 152 (1): 163-175.) for HLA-A of the EGFR binding domain of the Eps8 molecule * The 2402 restriction was used for predictive analysis, and the polypeptide whose amino acid sequence was shown as SEQ ID No: 1 was screened out, and recorded as Eps8-327. The polypeptide shown in SEQ ID No: 1 was synthesized by Hangzhou Zhongpei Biochemical Co., Ltd. according to the sequence provided by the inventor, using the ...

Embodiment 2

[0026] Example 2 [Induction of sensitized antigen-presenting cells (APC) in vitro]

[0027] Using peripheral blood mononuclear cell-derived dendritic cells (DCs) as APCs, DCs were induced in vitro referring to elsewhere (NakaharaS, et al. Cancer Res 2003 Jul 155, 63(14):4112-8). Specifically, healthy volunteers (HLA-A * 2402 positive) isolated mononuclear cells (PBMCs) from peripheral blood, and isolated original DC by the adherent method. 1000U / ml interleukin 4 (IL-4) culture medium. On day 7 of culture, cytokine-induced DCs were pulsed with each of the synthetic peptides (20 µg / ml) for 3 hours in a medium containing 3 µg / ml β2-microglobulin. The resulting cells expressed DC-associated molecules such as CD80, CD83, CD86 and HLA-II molecules on the cell surface (data not shown).

Embodiment 3

[0028] Example 3 (induction of CTL in vitro)

[0029] The DCs pulsed with the polypeptide were inactivated with mitomycin C (MMC) (30 μg / ml, 30 min), and mixed with autologous CD8 at a ratio of 1:20. + T cells (obtained by positive selection from CD8 positive isolation kit) were mixed and cultured in medium containing IL-7 10ng / ml. On day 3, IL-2 was added to the medium to a final concentration of 20 U / ml. On days 7 and 14, T cells were further stimulated with peptide-pulsed, inactivated autologous DCs. On day 21, cells were collected to detect CTL function (OlsonBM, et al. Cancer Immunol Immunother 2011; 60(6): 781-792; Andersen RS, et al. Cancer Immunol Immunother 2011; 60(2): 227-234.).

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Abstract

The invention relates to a dual anti-tumor polypeptide based on the Eps8-EGFR binding domain. The amino acid sequence of the polypeptide is Glu-Phe-Leu-Asp-Cys-Phe-Gln-Lys-Phe (SEQ ID No:1). The dual anti-tumor polypeptide can induce toxic T cells, effectively kills HLA-A*2402 positive tumors and Eps8 positive tumors, can directly inhibit proliferation of HLA-A*2402 positive tumor cells and Eps8 positive tumor cells, and can be used for preparing dual anti-tumor medicine.

Description

technical field [0001] The invention relates to the field of organic chemistry, in particular to a polypeptide from mammals, which has anti-tumor activity and is suitable for preparing anti-tumor drugs. Background technique [0002] Peptide drugs have very important development value in clinical application. Some peptide drugs have the effect of promoting the immune function of the body, which are called peptide vaccines. The identification of novel tumor antigens that induce strong and specific antitumor immune responses warrants the development and clinical application of peptide vaccines against various types of tumors (Reche P, et al. J Immunol Res 2015; 2015:349049; Jazirehi AR, et al. al. Cancer Res 2011; 71(4):1406-1417; Andersen RS, et al. Cancer Immunol Immunother 2011; 60(2):227-234; Gritzapis AD, et al. Cancer Res 2010; 70(7):2686 -2696; Klepin HD, et al. Oncologist 2009; 14(3):222-232.). So far, there have been many clinical trials using tumor-associated antig...

Claims

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Application Information

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IPC IPC(8): C07K14/47A61K38/17A61P35/00
CPCA61K38/00C07K14/4748
Inventor 李玉华周炜均谢晓灵
Owner SOUTHERN MEDICAL UNIVERSITY
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