A dual antitumor polypeptide based on the EPS8-SH3 domain

An eps8-sh3, anti-tumor technology, applied in the field of preparing anti-tumor drugs, can solve the problems of low inhibition rate and unsatisfactory tumor cell proliferation inhibition effect.

Inactive Publication Date: 2019-05-03
SOUTHERN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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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  • A dual antitumor polypeptide based on the EPS8-SH3 domain
  • A dual antitumor polypeptide based on the EPS8-SH3 domain
  • A dual antitumor polypeptide based on the EPS8-SH3 domain

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1 (screening of Eps8-SH3 binding domain polypeptides)

[0024] The anti-tumor polypeptide derived from the Eps8-SH3 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 SH3 domain of the Eps8 molecule * 2402 restriction prediction analysis was carried out, and the polypeptide with the amino acid sequence shown in SEQ ID No: 1 was screened out, and recorded as Eps8-534. 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 Fmoc solid-phas...

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 (Olson BM, 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 an Eps8-SH3 structural domain-based dual antitumor polypeptide. The polypeptide has an amino acid sequence of Lys-Tyr-Ala-Lys-Ser-Lys-Tyr-Asp-Phe (SEQ ID No: 1). The dual antitumor polypeptide can induce cytotoxic T cells, effectively kill HLA-A*2402 positive and Eps8 positive tumors, directly inhibit HLA-A*2402 positive and Eps8 positive tumor cell proliferation and be used for preparation of dual antitumor drugs.

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 Res2015; 2015:349049; Jazirehi AR, et 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 antigen-de...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/47A61K38/17A61P35/00
CPCA61K38/00C07K14/47
Inventor 李玉华周炜均谢晓灵
Owner SOUTHERN MEDICAL UNIVERSITY
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