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New Targeted Therapeutic Strategies of Multiple Myeloma
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New Targeted Therapeutic Strategies of Multiple Myeloma

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 20 May 2024 | Viewed by 4083

Special Issue Editors

Dr. Grazia Galleri

E-Mail Website
Guest Editor
Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy
Interests: immunology and immunopathology; inflammation molecular mechanisms,T cell, cytokine, cell cicle, cytofluorimetry, natural antioxidants drugs; oxidative stress; cell signaling cancer patway; molecular biology; apoptosis, neurodegenerative diseases
Prof. Dr. Maria Rosaria De Miglio

E-Mail Website
Guest Editor
Department of Medical, Surgical and Experimental Sciences, University of Sassari, Via P. Manzella 4, 07100 Sassari, Italy
Interests: cancer transcriptome; cancer genetics and epigenetics; cancer metabolism; colorectal carcinoma; “triple negative” breast cancer; clear cell renal carcinoma; precision medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Multiple myeloma (MM) is a hematologic neoplasm of plasma cells residing in the bone marrow. This dysregulatory disease of proliferation in the bone marrow has remained largely incurable despite the fact that treatment options have increased significantly over the past 10 years, imparting dramatic improvements in patients' life expectancy in the era of myeloma-targeted immunomodulatory agents. Several factors can determine the treatment of multiple myeloma, such as age and general health status, laboratory and cytogenetic (genomic) test results, and symptoms and complications of the disease. In addition, plasma cells, among other things, activate a process of bone erosion, thus creating significant damage typical of this disease. Bone lesions are often so significant that they do not regress even when the disease is in remission.

The standard treatment of basic myeloma consists of high-dose chemotherapy in combination with autologous stem cell transplantation (ASCT). Recent studies suggest that ASCT restores immune balance and represents a logical platform in which to intervene to prevent immune escape, since immunotherapy appears largely ineffective once disease progression is established. In fact, this is largely underpinned by depletion of T cells, which had initially recognized the myeloma and a suppressive bone marrow microenvironment. New immunotherapies based on checkpoint inhibition targeting the immune receptor TIGIT and deletion of suppressive myeloid populations appear attractive, especially after ASCT.

This special issue on "Novel Targeted Therapeutic Strategies of Multiple Myeloma" welcomes original research articles that illustrate and stimulate growing efforts to understand the implications of using novel natural and engineered molecules or compounds that enhance the bone marrow microenvironment disrupted by cytoreduction, including depletion and priming of T cells through immunogenic cell death and inflammation. Research articles studying the 'interaction of these compounds/drugs with the immunologically favorable environment of ASCT transplantation or reducing the impact of plasma cells on bone degradation are also particularly appreciated. We also appreciate the submission of review articles that critically assess and discuss the current state of the art concerning the highlighted topics.

Dr. Grazia Galleri
Prof. Dr. Maria Rosaria De Miglio
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • multiple myeloma
  • uncontrolled proliferation
  • plasmacells
  • immunoglobulins
  • natural drug therapies
  • immunotherapy
  • B cells
  • T cells
  • immunosuppressive cells
  • chemotherapeutics
  • molecular checkpoints
  • stem cell transplantation (ASCT)
  • current status in MM therapy
  • new immunomodulatory drug/nutural compounds
  • monoclonal antibodies
  • osteoclast activity and bone resorption

Published Papers (2 papers)

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Research

21 pages, 3731 KiB  
Article
Nicotinamide-Expanded Allogeneic Natural Killer Cells with CD38 Deletion, Expressing an Enhanced CD38 Chimeric Antigen Receptor, Target Multiple Myeloma Cells
by Avishay Edri, Nimrod Ben-Haim, Astar Hailu, Nurit Brycman, Orit Berhani-Zipori, Julia Rifman, Sherri Cohen, Dima Yackoubov, Michael Rosenberg, Ronit Simantov, Hideshima Teru, Keiji Kurata, Kenneth Carl Anderson, Ayal Hendel, Aviad Pato and Yona Geffen
Int. J. Mol. Sci. 2023, 24(24), 17231; https://doi.org/10.3390/ijms242417231 - 07 Dec 2023
Viewed by 1832
Abstract
Natural killer (NK) cells are a vital component of cancer immune surveillance. They provide a rapid and potent immune response, including direct cytotoxicity and mobilization of the immune system, without the need for antigen processing and presentation. NK cells may also be better [...] Read more.
Natural killer (NK) cells are a vital component of cancer immune surveillance. They provide a rapid and potent immune response, including direct cytotoxicity and mobilization of the immune system, without the need for antigen processing and presentation. NK cells may also be better tolerated than T cell therapy approaches and are susceptible to various gene manipulations. Therefore, NK cells have become the focus of extensive translational research. Gamida Cell’s nicotinamide (NAM) platform for cultured NK cells provides an opportunity to enhance the therapeutic potential of NK cells. CD38 is an ectoenzyme ubiquitously expressed on the surface of various hematologic cells, including multiple myeloma (MM). It has been selected as a lead target for numerous monoclonal therapeutic antibodies against MM. Monoclonal antibodies target CD38, resulting in the lysis of MM plasma cells through various antibody-mediated mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis, significantly improving the outcomes of patients with relapsed or refractory MM. However, this therapeutic strategy has inherent limitations, such as the anti-CD38-induced depletion of CD38-expressing NK cells, thus hindering ADCC. We have developed genetically engineered NK cells tailored to treat MM, in which CD38 was knocked-out using CRISPR-Cas9 technology and an enhanced chimeric antigen receptor (CAR) targeting CD38 was introduced using mRNA electroporation. This combined genetic approach allows for an improved cytotoxic activity directed against CD38-expressing MM cells without self-inflicted NK-cell-mediated fratricide. Preliminary results show near-complete abolition of fratricide with a 24-fold reduction in self-lysis from 19% in mock-transfected and untreated NK cells to 0.8% of self-lysis in CD38 knock-out CAR NK cells. Furthermore, we have observed significant enhancements in CD38-mediated activity in vitro, resulting in increased lysis of MM target cell lines. CD38 knock-out CAR NK cells also demonstrated significantly higher levels of NK activation markers in co-cultures with both untreated and αCD38-treated MM cell lines. These NAM-cultured NK cells with the combined genetic approach of CD38 knockout and addition of CD38 CAR represent a promising immunotherapeutic tool to target MM. Full article
(This article belongs to the Special Issue New Targeted Therapeutic Strategies of Multiple Myeloma)
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14 pages, 7484 KiB  
Article
Study on the Effect of EZH2 Inhibitor Combined with TIGIT Monoclonal Antibody against Multiple Myeloma Cells
by Zhaoyun Liu, Yue Jia, Chun Yang, Hui Liu, Hongli Shen, Hao Wang and Rong Fu
Int. J. Mol. Sci. 2023, 24(10), 8603; https://doi.org/10.3390/ijms24108603 - 11 May 2023
Cited by 2 | Viewed by 1537
Abstract
EZH2, a member of the polycomb repressive complex 2, induces trimethylation of the downstream gene at the histone three lysine 27 (H3K27me3) position to inhibit tumor cell proliferation. Here, we showed that the apoptosis rate and apoptotic protein expression increased after EZH2 inhibition, [...] Read more.
EZH2, a member of the polycomb repressive complex 2, induces trimethylation of the downstream gene at the histone three lysine 27 (H3K27me3) position to inhibit tumor cell proliferation. Here, we showed that the apoptosis rate and apoptotic protein expression increased after EZH2 inhibition, whereas key molecules of the NF-κB signaling pathway and the downstream target genes were inhibited. Additionally, the expression of CD155, a TIGIT high-affinity ligand in multiple myeloma (MM) cells, was decreased by the mTOR signaling pathway. Furthermore, the combination of EZH2 inhibitor and TIGIT monoclonal antibody blockade enhanced the anti-tumor effect of natural killer cells. In summary, the EZH2 inhibitor not only plays an anti-tumor role as an epigenetic drug, but also enhances the anti-tumor effect of the TIGIT monoclonal antibody by affecting the TIGIT-CD155 axis between NK cells and MM cells, thus providing new ideas and theoretical basis for the treatment of MM patients. Full article
(This article belongs to the Special Issue New Targeted Therapeutic Strategies of Multiple Myeloma)
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