Identification of an immunogenic DKK1 long peptide for immunotherapy of human multiple myeloma.

Identification of an immunogenic DKK1 long peptide for immunotherapy of human multiple myeloma. Haematologica. 2020 Feb 20;: Authors: Li R, Zheng C, Wang Q, Bi E, Yang M, Hou J, Fu W, Yi Q, Qian J Abstract Dickkopf-1 (DKK1), broadly expressed by tumor cells from human multiple myeloma (MM) and other cancers but absent from most normal tissues, may be an ideal target for immunotherapy. Our previous studies have shown that DKK1 (peptide)-specific cytotoxic T lymphocytes can effectively lyse primary MM cells in vitro. To develop DKK1-based vaccines that can be easily and inexpensively made and used by all patients, we identified a DKK1 long peptide (LP), DKK13-76-LP, that contains 74 amino acids and epitopes that can potentially bind to all major MHC class I and II molecules. Using HLA-A*0201- and HLA-DR*4-transgenic mouse models, we found that DKK1-specific CD4+ and CD8+ T cell responses, detected by DKK1 short peptide (P20 and P66v)-HLA-A*0201 tetramer staining and cytotoxic assay for CD8+ T cells or by CSFE dilution and IFN-a; secretion for CD4+ T cells respectively, can be induced in vivo by immunizing mice with the DKK13-76-LP. In addition, DKK13-76-LP also induced anti-DKK1 humoral immunity in the transgenic mice and the DKK1 antibodies were functional. Finally, DKK13-76-LP stimulated human blood T cells ex vivo to generate DKK1-specific CD4+ and CD8+ T cell responses from eight out of ten MM patients with different MHC backgrounds. The generated DKK1...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research

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Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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Source: Johnson and Johnson - Category: Pharmaceuticals Tags: Innovation Source Type: news
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Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
CONCLUSIONS: Our findings demonstrate that somatic mutations in multiple myeloma can be immunogenic and induce neoantigen-specific T-cell activation that is associated with antitumor activity in vitro and clinical response in vivo. Our results provide the foundation for using neoantigen targeting strategies such as peptide vaccines in future trials for patients with multiple myeloma. PMID: 31857430 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
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Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
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Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
This study has implications in increasing the efficacy of cancer immunotherapy in MM.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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