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  1. Article: Checkpoint inhibition in hematologic malignancies.

    Tsumura, Aaron / Levis, Daniel / Tuscano, Joseph M

    Frontiers in oncology

    2023  Volume 13, Page(s) 1288172

    Abstract: Checkpoint inhibitor therapy has emerged as an effective therapeutic strategy for many types of malignancies, especially in solid tumors. Within the last two decades, numerous monoclonal antibody drugs targeting the CTLA-4 and PD-1/PD-L1 checkpoint ... ...

    Abstract Checkpoint inhibitor therapy has emerged as an effective therapeutic strategy for many types of malignancies, especially in solid tumors. Within the last two decades, numerous monoclonal antibody drugs targeting the CTLA-4 and PD-1/PD-L1 checkpoint pathways have seen FDA approval. Within hematologic malignancies, Hodgkin Lymphoma has seen the greatest clinical benefits thus far with more recent data showing efficacy in the front-line setting. As our understanding of checkpoint inhibition expands, using these pathways as a therapeutic target has shown some utility in the treatment of other hematologic malignancies as well, primarily in the relapsed/refractory settings. Checkpoint inhibition also appears to have a role as a synergistic agent to augment clinical responses to other forms of therapy such as hematopoietic stem cell transplant. Moreover, alternative checkpoint molecules that bypass the well-studied CTLA-4 and PD-1/PD-L1 pathways have emerged as exciting new therapeutic targets. Most excitingly is the use of anti-CD47 blockade in the treatment of high risk MDS and TP-53 mutated AML. Overall, there has been tremendous progress in understanding the benefits of checkpoint inhibition in hematologic malignancies, but further studies are needed in all areas to best utilize these agents. This is a review of the most recent developments and progress in Immune Checkpoint Inhibition in Hematologic Malignancies in the last decade.
    Language English
    Publishing date 2023-10-17
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2023.1288172
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A Novel bispecific T-cell engager (BiTE) targeting CD22 and CD3 has both in vitro and in vivo activity and synergizes with blinatumomab in an acute lymphoblastic leukemia (ALL) tumor model.

    Meckler, Joshua F / Levis, Daniel J / Vang, Daniel P / Tuscano, Joseph M

    Cancer immunology, immunotherapy : CII

    2023  Volume 72, Issue 9, Page(s) 2939–2948

    Abstract: Immunotherapy has revolutionized cancer therapy. Two recently FDA-approved immunotherapies for B-cell malignancies target CD19, in the form of a Bispecific T-Cell Engager (BiTE) antibody construct or chimeric antigen receptor T (CAR-T) cells. ... ...

    Abstract Immunotherapy has revolutionized cancer therapy. Two recently FDA-approved immunotherapies for B-cell malignancies target CD19, in the form of a Bispecific T-Cell Engager (BiTE) antibody construct or chimeric antigen receptor T (CAR-T) cells. Blinatumomab, an FDA-approved BiTE, binds to CD19 on B cells and to CD3 on T cells, mediating effector-target cell contact and T-cell activation that results in effective elimination of target B cells. Although CD19 is expressed by essentially all B-cell malignancies at clinical presentation, relapses with loss or reduction in CD19 surface expression are increasingly recognized as a cause of treatment failure. Therefore, there is a clear need to develop therapeutics for alternate targets. We have developed a novel BiTE consisting of humanized anti-CD22 and anti-CD3 single chain variable fragments. Target binding of the anti-CD22 and anti-CD3 moieties was confirmed by flow cytometry. CD22-BiTE promoted in vitro cell-mediated cytotoxicity in a dose and effector: target (E:T)-dependent fashion. Additionally, in an established acute lymphoblastic leukemia (ALL) xenograft mouse model, CD22-BiTE demonstrated tumor growth inhibition, comparable to blinatumomab. Further, the combination of blinatumomab and CD22-BiTE yielded increased efficacy in vivo when compared to the single agents. In conclusion, we report here the development of a new BiTE with cytotoxic activity against CD22
    MeSH term(s) Humans ; Animals ; Mice ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Antineoplastic Agents/therapeutic use ; T-Lymphocytes ; Antibodies, Bispecific/pharmacology ; Antibodies, Bispecific/therapeutic use ; Antigens, CD19
    Chemical Substances blinatumomab (4FR53SIF3A) ; Antineoplastic Agents ; Antibodies, Bispecific ; Antigens, CD19
    Language English
    Publishing date 2023-05-29
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 195342-4
    ISSN 1432-0851 ; 0340-7004
    ISSN (online) 1432-0851
    ISSN 0340-7004
    DOI 10.1007/s00262-023-03444-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A Fermented Wheat Germ Extract Contains Protein Components Active against NSCLC Xenografts In Vivo.

    Levis, Daniel J / Meckler, Joshua F / O'Donnell, Robert T / Tuscano, Joseph M

    Current issues in molecular biology

    2023  Volume 45, Issue 9, Page(s) 7087–7096

    Abstract: Non-small cell lung cancer (NSCLC) continues to be the leading cause of cancer-related deaths. Although advances have been made in the past decade to treat such tumors, most options induce multiple side effects, and many patients discontinue therapy due ... ...

    Abstract Non-small cell lung cancer (NSCLC) continues to be the leading cause of cancer-related deaths. Although advances have been made in the past decade to treat such tumors, most options induce multiple side effects, and many patients discontinue therapy due to toxicity. Thus, the need remains for non-toxic, effective NSCLC therapies, especially in an elderly patient population. Our lab has previously identified a protein fraction from the nutraceutical Avemar
    Language English
    Publishing date 2023-08-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2000024-8
    ISSN 1467-3045 ; 1467-3037
    ISSN (online) 1467-3045
    ISSN 1467-3037
    DOI 10.3390/cimb45090448
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A look into the future of blockchain technology.

    Levis, Daniel / Fontana, Francesco / Ughetto, Elisa

    PloS one

    2021  Volume 16, Issue 11, Page(s) e0258995

    Abstract: In this paper, we use a Delphi approach to investigate whether, and to what extent, blockchain-based applications might affect firms' organizations, innovations, and strategies by 2030, and, consequently, which societal areas may be mainly affected. We ... ...

    Abstract In this paper, we use a Delphi approach to investigate whether, and to what extent, blockchain-based applications might affect firms' organizations, innovations, and strategies by 2030, and, consequently, which societal areas may be mainly affected. We provide a deep understanding of how the adoption of this technology could lead to changes in Europe over multiple dimensions, ranging from business to culture and society, policy and regulation, economy, and technology. From the projections that reached a significant consensus and were given a high probability of occurrence by the experts, we derive four scenarios built around two main dimensions: the digitization of assets and the change in business models.
    MeSH term(s) Blockchain ; Delphi Technique ; Geography ; Humans ; Surveys and Questionnaires ; Technology
    Language English
    Publishing date 2021-11-17
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0258995
    Database MEDical Literature Analysis and Retrieval System OnLINE

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