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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(The Mount Sinai Hospital / Mount Sinai School of Medicine) Researchers at the Icahn School of Medicine at Mount Sinai have discovered a way to move precision immunotherapy forward by using genomics to inform immunotherapy for multiple myeloma, a blood cancer, according to a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research, in December.
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
Inokuchi Despite therapeutic advances over the past decades, multiple myeloma (MM) remains a largely incurable disease with poor prognosis in high-risk patients, and thus new treatment strategies are needed to achieve treatment breakthroughs. MM represents various forms of impaired immune surveillance characterized by not only disrupted antibody production but also immune dysfunction of T, natural killer cells, and dendritic cells, although immunotherapeutic interventions such as allogeneic stem-cell transplantation and dendritic cell-based tumor vaccines were reported to prolong survival in limited populations of MM p...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Cancer immunotherapies have primarily focused on generating tumoricidal CD8 T cells. However, recent data demonstrate a critical role for CD4 T cells in tumor immunity. CD4 T cells against epitopes derived from mutated tumor-associated neo-antigens (neoAg) conferred protection against tumor growth in animal models of neoAg vaccine therapy. In clinical studies, immunity elicited by neoAg vaccines was associated with improved survival, even though the majority of immune responses were CD4 T cells that did not have cytolytic activity.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
This article introduces the main concepts and addresses the most relevant clinical modalities of cellular immunotherapies for hematological malignancies: antigen non-specific T cell therapy, genetically modified T cell receptor (TCR) T cell therapy, chimeric antigen receptor (CAR) T cell therapy, and CAR-T cell clinical trials in leukemia, lymphoma, and multiple myeloma. Clinical trials have shown encouraging results, but future studies may need to incorporate novel CAR constructs or targets with enhanced safety and efficacy to ensure long-term benefits. PMID: 31338822 [PubMed - in process]
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Multiple myeloma (MM) is an incurable hematological malignancy. Immunodeficiency results in the incapability of immunity to eradicate both tumor cells and pathogens. Immunotherapies along with antibiotics and other anti-infectious agents are applied as substitutes for immunity in MM. Immunotherapies including monoclonal antibodies, immune checkpoints inhibitors, affinity- enhanced T cells, chimeric antigen receptor T cells and dendritic cell vaccines are revolutionizing MM treatment. By suppressing the pro-inflammatory milieu and pathogens, prophylactic and therapeutic antibiotics represent anti-tumor and anti-infection pr...
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
Conclusion MTDH is pro-oncogenic factor playing multifaceted and diverse roles in cancer progression. Its association and central role in regulating signaling pathways such a MAPK, wnt/β-catenin, PI3K/AkT, NF-κβ pathways in various cancers shows that it plays a vital role in metastasis. MTDH contribution to chemo and radiotherapy resistance provides a new direction for the development of anticancer therapeutics. Multiple mechanisms converge to promote expression of MTDH in cancers. Further studies are therefore warranted to determine whether the elevated MTDH expression has prognostic value for development...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Hui Zhou, Xiaoyan Fu, Qian Li and Ting Niu* Department of Hematology and Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu, China Background: Immune checkpoint inhibition therapy with monoclonal antibody against programmed cell death protein 1 (PD-1), including nivolumab and pembrolizumab, has demonstrated powerful clinical efficacy in the treatment of advanced cancers. However, there is no evidence-based systematic review on the safety and efficacy of anti-PD-1 antibody in treating lymphoma. Methods: To evaluate the safety and efficacy of nivolumab/pembrolizumab, we analyzed clin...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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