XBP1, CD138, and CS1 peptides

A composition and drug technology, applied in the fields of peptides, specific peptides, peptide/protein components, etc., can solve problems such as poor prognosis of patients

Active Publication Date: 2014-05-21
DANA FARBER CANCER INST INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although both conditions are often treated with, for example, chemotherapy alone or in combination with bone marrow transplantation, patients suffering from either of these conditions often have a poorer prognosis

Method used

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  • XBP1, CD138, and CS1 peptides
  • XBP1, CD138, and CS1 peptides
  • XBP1, CD138, and CS1 peptides

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0231] Example 1: Materials and methods

[0232] cell line. Human multiple myeloma cell lines: McCAR, MM1S and U226 were obtained from the American Type Culture Collection (ATCC; Manassas, VA). The human acute myeloid leukemia (AML) cell line ML-2 was kindly provided by Dr. Y Matsuo (Fujisaki Cell Center, Okayama, Japan). The T2 cell line, which is a hybrid of human B and T cells expressing the HLA-A2.1 molecule (Zweerink et al., (1993) J Immunol. 150(5): 1763-71), was developed by Dr.J.Molldrem (University of Texas M.D. Anderson Cancer Center, Houston, TX) and was used as a source of antigen presenting cells (APCs). All cell lines were cultured in RPMI-1640 medium (Gibco-Life Technologies, Rockville, MD).

[0233] Reagent . Mouse anti-human CD80 or CD83 monoclonal antibody (mAb) conjugated to phycoerythrin (PE) was purchased from Immunotech (Hialeigha, FL). Specific for CD3, CD4, CD8, CD14, CD40, CD45RA, CD45RO, CD69, CD80, CD83, CD86, CCR7, HLA-A2, and HLA-DR conju...

Embodiment 2

[0249] Example 2: XBP1 184-192 (NISPWILAV) and spliced ​​XBP1 367-145 (ELFPQLISV) Peptide Display High affinity / stability for HLA-A2 binding

[0250] The full-length sequence of unspliced ​​or spliced ​​XBP1 protein (see above) was analyzed to predict specificity for HLA-A2 using the search software SYFPEITHI (database of MHC ligands and peptide motifs, Institute for Cell Biology, Department of Immunology, Heidlberg) Peptides that were neutral were followed by the BIMAS program to select peptides with prolonged half-time off-rates. A total of six potential HLA-A2 binding native peptides were selected from the unspliced ​​XBP1 protein, as follows: XBP1 117-125 (LLREKTHGL (SEQ ID NO: 1); XBP1 #1 peptide), XBP1 184-192 (NISPWILAV (SEQ ID NO: 2); XBP1 #2 peptide), XBP1 189-197 (ILAVLTLQI (SEQ ID NO: 3); XBP1 #3 peptide), XBP1 192-200(ILAVLTLQI (SEQ ID NO: 4); XBP1 #4 peptide), XBP1 110-118 (KLLLENQLL (SEQ ID NO: 5); XBP1 #5 peptide), and XBP1 93-101 (RMSELEQQV (...

Embodiment 3

[0254] Example 3: XBP1-CTLs display a distinct phenotype from unstimulated T cells

[0255] Cytotoxic T lymphocytes (CTLs) are phenotypically defined by the expression of unique cell surface antigens such as CD8. Cell surface antigens can also be used to further define CTLs as naive or activated memory cells. For example, naïve human CTL can pass CD45RA + / CCR7 + is defined by the presence of CD69, while activated human memory cells can be defined as CD69 + / CD45RO + to identify. Flow cytometry was performed on scrambled peptide-stimulated human T cell populations to determine the percentage of naive or activated memory cells in CTL. Figure 5 showed that CTLs stimulated with XBP1 irregular peptides induced a significantly higher percentage of CD8 compared to unstimulated T cell cultures (33%) + T cells (unspliced ​​peptide stimulated: 81%; spliced ​​peptide stimulated: 75%), and a lower percentage of CD4 compared to unstimulated T cell cultures (64%) + T cells (unspl...

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PUM

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Abstract

Various features are disclosed herein, including immunogenic XBP1-, CD138-, and CS1-derived peptides (and pharmaceutical compositions thereof), among others. The peptides can be used in a variety of methods, such as for inducing an immune response, for generating antibodies, and for treating cancer (e.g. plasma cell disorders such as multiple myeloma or Waldenstrom's macroglobulinemia) approach. The peptides can also be included in MHC molecule multimer compositions, and can also be used, for example, in methods for detecting T cells in a population of cells.

Description

[0001] Statement Regarding Federally Sponsored Research or Development [0002] Research described in this application was supported by Grant Nos. P50-100707, PO1-78378, and RO1-50947, each from the National Institutes of Health (USA). Accordingly, the Government has certain rights in this invention. Background of the invention [0003] Multiple myeloma and Waldenstrom's macroglobulinemia are two blood cancers that affect approximately 45,000 and 1,500 people, respectively, in the United States each year. Although both conditions are often treated with, for example, chemotherapy alone or in combination with bone marrow transplantation, patients suffering from either of these conditions generally have a poorer prognosis. Therefore, effective therapeutic and / or prophylactic regimens are urgently needed. Summary of the invention [0004] The present disclosure relates to immunogenic X-box protein 1 (XBP1), CD138, and CD2 subset 1 (CS1) derived peptides and methods of using th...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/00
CPCA61K38/00C07K14/70507C07K14/4702A61P35/00A61P35/02A61P37/04A61P43/00A61K2039/804A61K39/0011Y02A50/30A61K2039/55516A61K2039/55566
Inventor 尼基尔.C.穆恩希肯尼斯.C.安德森裵洙恩
Owner DANA FARBER CANCER INST INC
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