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Cytotoxin T lymphocyte

A lymphocyte and cytotoxic technology, applied in the field of treatment and diagnosis, can solve the problems of backward analysis and research, CTL that is difficult to provide tumor treatment, etc.

Inactive Publication Date: 2002-11-13
TAKARA HOLDINGS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] As far as the current situation is concerned, the above-mentioned restricted antigenic peptides caused by HLA-A24, such as MAGE-1, MAGE-2, MAGE-3, CEA, HER2 / neu, tyrosinase, β-catenin (β-catenin) etc., but compared with HLA-A2.1, their analytical research is still very backward, and it is extremely necessary to discover new antigenic peptides for various tumor antigens
In addition, research on CTLs with tumor cell-specific effects on Asians, especially Japanese, is also backward, and it is difficult to provide CTLs suitable for tumor therapy

Method used

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  • Cytotoxin T lymphocyte
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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0144] Example 1 Preparation of PSMA Antigen Peptide-Specific CTL

[0145] In this example, CTLs were prepared by the induction method using dendritic cells (DC) for antigen presentation.

[0146] (1) Screening and synthesis of peptides for CTL induction

[0147] For the amino acid sequence of the PSMA protein composed of 750 amino acids, the peptide with the HLA-A24 binding motif structure (the second amino acid residue at the N-terminal is selected from Tyr, Phe, Trp and Met, and the amino acid residue at the C-terminal Selected from Leu, Ile, Phe and Trp) as the center, screen 9 peptides shown in Table 1 as candidate peptides of PSMA antigenic peptides.

[0148] serial number

Position in PSMA

name

10

298-306

PSMA24-1

11

624-632

PSMA24-2

1

227-235

PSMA24-3

12

606-614

PSMA24-4

2

178-186

PSMA24-5

13

74-83

PSMA24-6

14

565-574

PSMA24-7

...

Embodiment 2

[0173] Example 2 Preparation of PSMA Antigenic Peptide Functional Derivatives

[0174] (1) Synthesis of PSMA24-5 variants

[0175] serial number

name

8

PSMA24-5-1A

17

PSMA24-5-4A

9

PSMA24-5-5A

18

PSMA24-5-6A

19

PSMA24-5-7A

20

PSMA24-5-8A

5

PSMA24-5-9L

[0176] A total of seven peptides, PSMA24-5-1A to PSMA24-5-9L shown in Table 2, were prepared with a peptide synthesizer.

[0177] (2) Identification of functional derivatives of PSMA24-5

[0178] It was checked whether the CTL obtained in Example 1 above, which can recognize the complex of PSMA24-5 and HLA-A24 molecule, can recognize the complex of the peptide shown in Table 2 and HLA-A24 molecule.

[0179] First, for the CTL that can recognize PSMA24-5 prepared by the same method as in Example 1 (2), for 51 Cr-labeled TISI (-) cells, and 7 kinds of peptides selected from PSMA24-5-1A~PSMA24-5-9L and p...

Embodiment 3

[0181] Example 3 Using adenovirus to evaluate CTL

[0182] (1) Preparation of genes from adenovirus into target cells

[0183] As target cells endogenously presenting antigens, tumor cells expressing HLA-A24 and PSMA were constructed. That is, for the prostate cancer cell line LNCaP cells expressing PSMA but not expressing HLA-A24, the gene was introduced into the cells with an HLA-A24 gene-transforming adenovirus vector. For cancer cells MKN45, 888mel, SW480, and T.T that express HLA-A24 but do not express PSMA, the PSMA gene is introduced into the cells with an adenoviral vector that transduces the PSMA gene.

[0184] The transgenic adenoviral vector was prepared according to the COS-TPC method.

[0185] First, place the 5×10 5 4ml of cell suspension per ml was inoculated in a 6-well cell culture plate and cultured overnight. After culturing, the above cells were infected with HLA-A24 gene-transformed adenovirus, PSMA gene-transformed adenovirus or non-transformed adenov...

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PUM

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Abstract

PURPOSE: Provided are a method and a substance useful for treatment and diagnosis of prostate cancer. Particularly, provided are a peptide having a specific sequence, a mutant thereof and a nucleic acid encoding the same. CONSTITUTION: An HLA-A24- restricted antigen peptide is characterized by being capable of inducing a CTL(cytotoxic lymphocyte) having a T cell receptor specifically recognizing a cell manifesting on the cell surface a complex between the peptide and HLA(human main histocompatibility antigen)-A24 molecule.

Description

technical field [0001] The present invention relates to a technique useful in the treatment and diagnosis of diseases caused by abnormal expression of prostate specific membrane antigen (prostate specific membrane antigen, hereinafter abbreviated as PSMA), such as cancer, and specifically, prostate cancer. More specifically, the present invention relates to a compound having a recognizable antigenic peptide and a human major histocompatibility antigen (HLA) molecule useful in the treatment and diagnosis of cancer, specifically prostate cancer and other cancers with abnormal expression of PMSA. Cytotoxic T lymphocytes (cytotoxic T lymphocytes, hereinafter abbreviated as CTL) of the T cell receptor, the antigenic peptide, a CTL inducer useful for inducing the CTL, etc., a method for inducing the CTL, and an anticancer drug useful for the above-mentioned cancer , the detection method of the CTL sensitive cell and its detection reagent, the detection method of the HLA-A24 molecule...

Claims

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Application Information

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IPC IPC(8): C07K7/06A61K38/17A61P35/00C07K14/435C07K14/47C12N5/08C12N15/12C12Q1/04G01N33/68
CPCA61K35/17A61K38/08C07K7/06C12N15/861
Inventor 糠谷育卫冈泽一秀川嶋一郎黑目彻竹迫一任加藤郁之进
Owner TAKARA HOLDINGS
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