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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: A phase II trial of decitabine, bortezomib and pegylated liposomal doxorubicin for the treatment of relapsed or refractory AML.

    Jonas, Brian A / Potter, Laura A / Galkin, Maria / Tuscano, Joseph M

    Leukemia research reports

    2023  Volume 19, Page(s) 100374

    Language English
    Publishing date 2023-06-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2706248-X
    ISSN 2213-0489
    ISSN 2213-0489
    DOI 10.1016/j.lrr.2023.100374
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. 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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  4. Article ; Online: A Systematic Review of Clinical Applications of Anti-CD20 Radioimmunotherapy for Lymphoma.

    Durando, Michael / Gopal, Ajay K / Tuscano, Joseph / Persky, Daniel

    The oncologist

    2024  Volume 29, Issue 4, Page(s) 278–288

    Abstract: Purpose: The clinical efficacy of anti-CD20 radioimmunotherapy (RIT) is due to a combination of extracellular mechanisms involving immune-mediated cytotoxicity, and intracellular mechanisms related to inhibition of CD20 signaling and DNA damage from ... ...

    Abstract Purpose: The clinical efficacy of anti-CD20 radioimmunotherapy (RIT) is due to a combination of extracellular mechanisms involving immune-mediated cytotoxicity, and intracellular mechanisms related to inhibition of CD20 signaling and DNA damage from ionizing radiation. In 2002, the first RIT was approved by the U.S. Food and Drug Administration for the treatment of patients with indolent B-cell follicular non-Hodgkin lymphoma (NHL). The 2 approved agents, 90 Y-ibritumomab tiuxetan (90Y-IT, Zevalin, Acrotech Biopharma) and 131 I-tositumomab (131-IT, Bexxar, GlaxoSmithKline) both target CD20. The aim of this study was to review the clinical applications and supporting clinical trial data of anti-CD20 RIT for lymphoma.
    Methods: A review of published articles and abstracts on the clinical efficacy and safety of 90Y-IT and iodine I 131 tositumomab was performed.
    Results: The clinical efficacy and safety of anti-CD20 RIT have been demonstrated in numerous clinical trials and case series. Agents have produced significant responses in patients with follicular NHLs and in off-label applications. Importantly, RIT has demonstrated promising findings in high-risk lymphomas and heavily pretreated and refractory patient populations. Associated toxicity profiles are noted as tolerable, acceptable, and most often reversible.
    Conclusions: In the 2 decades since its approval, anti-CD20 RIT continues to demonstrate efficacy, particularly with a proportion of patients maintaining long-term remissions. The combination of prolonged efficacy, tolerability, and treatment convenience makes RIT a reasonable alternative to other systemic therapies. It is recommended that further research on RIT should focus on biomarkers of long-term response, pretargeting, and sequencing of RIT in the treatment course.
    MeSH term(s) Humans ; Radioimmunotherapy ; Yttrium Radioisotopes/therapeutic use ; Lymphoma, Non-Hodgkin/drug therapy ; Lymphoma, Non-Hodgkin/radiotherapy ; Lymphoma, B-Cell/drug therapy
    Chemical Substances Yttrium-90 (1K8M7UR6O1) ; Yttrium Radioisotopes
    Language English
    Publishing date 2024-01-18
    Publishing country England
    Document type Systematic Review ; Journal Article
    ZDB-ID 1409038-7
    ISSN 1549-490X ; 1083-7159
    ISSN (online) 1549-490X
    ISSN 1083-7159
    DOI 10.1093/oncolo/oyad333
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. 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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  6. Article ; Online: Phase I trial of the combination of ibrutinib and lenalidomide of the treatment of patients with MDS who have failed standard therapy or who are unfit for or refuse standard therapy.

    Fisch, Samantha C / Tuscano, Joseph M / Qi, Lihong / Jonas, Brian A

    Leukemia research

    2022  Volume 122, Page(s) 106947

    MeSH term(s) Humans ; Lenalidomide ; Piperidines ; Adenine ; Chromosome Deletion
    Chemical Substances Lenalidomide (F0P408N6V4) ; ibrutinib (1X70OSD4VX) ; Piperidines ; Adenine (JAC85A2161)
    Language English
    Publishing date 2022-09-06
    Publishing country England
    Document type Clinical Trial, Phase I ; Letter
    ZDB-ID 752396-8
    ISSN 1873-5835 ; 0145-2126
    ISSN (online) 1873-5835
    ISSN 0145-2126
    DOI 10.1016/j.leukres.2022.106947
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Research Review: A systematic review and meta-analysis of infant and toddler temperament as predictors of childhood attention-deficit/hyperactivity disorder.

    Joseph, Heather M / Lorenzo, Nicole E / Fisher, Nadiyah / Novick, Danielle R / Gibson, Cassandra / Rothenberger, Scott D / Foust, Jill E / Chronis-Tuscano, Andrea

    Journal of child psychology and psychiatry, and allied disciplines

    2023  Volume 64, Issue 5, Page(s) 715–735

    Abstract: Background: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with onset as early as preschool and impairment across the lifespan. Temperament factors, specifically those that theoretically map onto ADHD symptoms, ... ...

    Abstract Background: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with onset as early as preschool and impairment across the lifespan. Temperament factors, specifically those that theoretically map onto ADHD symptoms, may be early markers of risk for developing later childhood ADHD that could be identifiable in infancy or toddlerhood. This meta-analysis examined the associations between these early temperamental factors and later symptoms and diagnosis of ADHD and mapped early temperament constructs onto the three ADHD symptom dimensions.
    Methods: A systemic review of the literature was conducted to identify prospective longitudinal studies that included theoretically relevant temperament constructs (sustained attention, activity level, inhibition, and negative emotionality) examined from birth to 36 months old and ADHD (symptoms or diagnosis) in preschool or childhood. The association between each temperament construct and ADHD outcomes was examined using pooled standardized estimates in meta-analyses.
    Results: Forty-eight articles (n = 112,716 infants/toddlers) prospectively examined temperament and the relation to childhood ADHD symptoms or diagnosis. Activity level (k = 18) in infancy and toddlerhood was moderately associated with childhood ADHD (r = .39, CI = 0.27, 0.51, p < .001). Moderate effect sizes were also observed for sustained attention (k = 9; r = -.28, CI = -0.42, -0.12, p < .001) and negative emotionality (k = 33; r = .25, CI = 0.16, 0.34, p < .001) with ADHD. The specificity of each temperament construct for later ADHD symptom dimensions was such that activity level and negative emotionality were predictive of all three symptom dimensions (i.e., inattention, hyperactivity/impulsivity, and combined), whereas sustained attention was only associated with combined symptoms.
    Conclusions: Infant and toddler temperament is an early risk factor for the development of childhood ADHD that could be utilized for early intervention identification. Yet, this systematic review found that relatively few prospective longitudinal studies have examined sustained attention (k = 9) and inhibition (k = 15) in infancy and toddlerhood in relation to later ADHD highlighting the need for further research.
    MeSH term(s) Humans ; Infant ; Child, Preschool ; Attention Deficit Disorder with Hyperactivity/epidemiology ; Attention Deficit Disorder with Hyperactivity/diagnosis ; Temperament/physiology ; Prospective Studies ; Risk Factors
    Language English
    Publishing date 2023-01-04
    Publishing country England
    Document type Meta-Analysis ; Systematic Review ; Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 218136-8
    ISSN 1469-7610 ; 0021-9630 ; 0373-8086
    ISSN (online) 1469-7610
    ISSN 0021-9630 ; 0373-8086
    DOI 10.1111/jcpp.13753
    Database MEDical Literature Analysis and Retrieval System OnLINE

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

    Daniel J. Levis / Joshua F. Meckler / Robert T. O’Donnell / Joseph M. Tuscano

    Current Issues in Molecular Biology, Vol 45, Iss 448, Pp 7087-

    2023  Volume 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 ® —dubbed fermented wheat germ protein (FWGP)—with demonstrated efficacy in lymphoma models both in vitro and in vivo. Here, we show that FWGP also has anti-tumor activity in vitro and in vivo against lung cancer. In vitro cytotoxicity against multiple lung cancer cell lines yielded IC 50 values comparable to those previously established with the parent product, Avemar. Further, significant A549 xenograft growth inhibition occurred in athymic nu/nu mice receiving FWGP in both pre-radiated and non-radiated models when compared to the untreated control. Encouragingly, mice treated with FWGP experienced no toxicities as detected by weight reduction or blood chemistry analysis. These data support the further study of FWGP as a potential non-toxic therapy for lung cancer and other oncologic indications.
    Keywords non-small cell lung cancer (NSCLC) ; fermented wheat germ protein (FWGP) ; fermented wheat germ extract ; A549 ; non-toxic ; natural product ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2023-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Yttrium-90 ibritumomab tiuxetan plus ATG/TLI for allogeneic hematopoietic cell transplantation in non-Hodgkin lymphoma.

    Othman, Tamer / Lowsky, Robert / Richman, Carol / Hoeg, Rasmus / Abedi, Mehrdad / Tuscano, Joseph

    Bone marrow transplantation

    2023  Volume 58, Issue 10, Page(s) 1143–1145

    MeSH term(s) Humans ; Lymphoma, Non-Hodgkin/therapy ; Lymphoma, Non-Hodgkin/pathology ; Yttrium Radioisotopes/therapeutic use ; Hematopoietic Stem Cell Transplantation ; Radioimmunotherapy
    Chemical Substances Yttrium-90 (1K8M7UR6O1) ; ibritumomab tiuxetan (4Q52C550XK) ; Yttrium Radioisotopes
    Language English
    Publishing date 2023-06-30
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 632854-4
    ISSN 1476-5365 ; 0268-3369 ; 0951-3078
    ISSN (online) 1476-5365
    ISSN 0268-3369 ; 0951-3078
    DOI 10.1038/s41409-023-02025-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Belinostat in Relapsed/Refractory T-Cell Large Granular Lymphocyte Leukemia.

    Poh, Christina / Arora, Mili / Ghuman, Sudeep / Tuscano, Joseph

    Acta haematologica

    2020  Volume 144, Issue 1, Page(s) 95–99

    Abstract: T-cell large granular lymphocyte (LGL) leukemia is a rare indolent neoplasm primarily treated with immunosuppression. Few therapies and no consensus exist for the optimal treatment of T-cell LGL leukemia refractory to immunosuppressive therapy. Here, we ... ...

    Abstract T-cell large granular lymphocyte (LGL) leukemia is a rare indolent neoplasm primarily treated with immunosuppression. Few therapies and no consensus exist for the optimal treatment of T-cell LGL leukemia refractory to immunosuppressive therapy. Here, we report a case of relapsed/refractory T-cell LGL treated with belinostat. A 57-year-old male presented with lymphocytosis and anemia and was found to have T-cell LGL, requiring frequent packed red blood cell transfusions. He was initially treated with methotrexate with no response after 7 months. He was then switched to cyclosporine and cyclophosphamide and experienced transfusion independence for 42 months before disease relapse. He was then started on belinostat with noted subsequent transfusion independence for greater than 15 months to date and decreased disease involvement on bone marrow biopsy. To our knowledge, this is the first reported case of belinostat use in relapsed/refractory T-cell LGL leukemia which resulted in a durable clinical and biologic response.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers ; Biopsy ; Drug Resistance, Neoplasm ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylase Inhibitors/therapeutic use ; Humans ; Hydroxamic Acids/pharmacology ; Hydroxamic Acids/therapeutic use ; Leukemia, Large Granular Lymphocytic/diagnosis ; Leukemia, Large Granular Lymphocytic/drug therapy ; Male ; Middle Aged ; Recurrence ; Retreatment ; Sulfonamides/pharmacology ; Sulfonamides/therapeutic use ; Symptom Assessment ; Therapeutics ; Treatment Outcome
    Chemical Substances Antineoplastic Agents ; Biomarkers ; Histone Deacetylase Inhibitors ; Hydroxamic Acids ; Sulfonamides ; belinostat (F4H96P17NZ)
    Language English
    Publishing date 2020-04-29
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 80008-9
    ISSN 1421-9662 ; 0001-5792
    ISSN (online) 1421-9662
    ISSN 0001-5792
    DOI 10.1159/000506918
    Database MEDical Literature Analysis and Retrieval System OnLINE

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