ArticleJournal of hematology & oncology2017
Mesenchymal stromal cells as vehicles of tetravalent bispecific Tandab (CD3/CD19) for the treatment of B cell lymphoma combined with IDO pathway inhibitor D-1-methyl-tryptophan.
Article in Journal of hematology & oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 89 citations in OpenAlex.
- Advances in the clinical application of mesenchymal stem cells for neurological disorders.Stem cell research & therapy · 2026Review
- Treatment of Mesenchymal Stem Cell-Derived Extracellular Vesicles with Extract of CulturedCurrent issues in molecular biology · 2026Article
- Tryptophan metabolism in tumor immune escape: mechanisms, cellular crosstalk, and therapeutic opportunities.Frontiers in immunology · 2026Review
- The roles and clinical applications of mesenchymal stem cells and their exosomes in hematologic diseases.Stem cell research & therapy · 2025Review
- Review
- Enhance therapeutic efficacy of BiTE (HER2/CD3) for HER2- positive tumors throughInternational journal of pharmaceutics: X · 2025Article
- Practical microenvironment classification in diffuse large B cell lymphoma using digital pathology.Cell reports. Medicine · 2025Article
- Construction of tetravalent bispecific Tandab (CD3/BCMA)-secreting human umbilical cord mesenchymal stem cells and its efficiency in the treatment of multiple myeloma.Stem cell research & therapy · 2025Article
- Metabolic-immune axis in the tumor microenvironment: a new strategy for prognostic assessment and precision therapy in DLBCL and FL.Frontiers in immunology · 2025Review
- Use of regulatory cells for achieving functional tolerance of pig heart xenotransplants in humans: a literature review.Frontiers in immunology · 2025Review
- Systemic administration of mesenchymal stem cells loaded with a novel oncolytic adenovirus carrying a bispecific T cell engager against hepatocellular carcinoma.Oncoimmunology · 2023Article
- Systematic comparation of the biological and transcriptomic landscapes of human amniotic mesenchymal stem cells under serum-containing and serum-free conditions.Stem cell research & therapy · 2022Article
- Multifaceted characterization of the biological and transcriptomic signatures of natural killer cells derived from cord blood and placental blood.Cancer cell international · 2022Article
- Construction of tandem diabody (IL-6/CD20)-secreting human umbilical cord mesenchymal stem cells and its experimental treatment on diffuse large B cell lymphoma.Stem cell research & therapy · 2022Article
- Application of Perinatal Derivatives on Oncological Preclinical Models: A Review of Animal Studies.International journal of molecular sciences · 2022Review
- Immunotherapy by mesenchymal stromal cell delivery of oncolytic viruses for treating metastatic tumors.Molecular therapy oncolytics · 2022Review
- Decoding the multidimensional signatures of resident and expanded natural killer cells generated from perinatal blood.American journal of cancer research · 2022Article
- Methods and criteria for validating the multimodal functions of perinatal derivatives when used in oncological and antimicrobial applications.Frontiers in bioengineering and biotechnology · 2022Review
- Research and Clinical Landscape of Bispecific Antibodies for the Treatment of Solid Malignancies.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Bone marrow-derived mesenchymal stem/stromal cells in patients with acute myeloid leukemia reveal transcriptome alterations and deficiency in cellular vitality.Stem cell research & therapy · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough blinatumomab, a bispecific T cell engaging antibody, exhibits high clinical response rates in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (B-ALL) and B cell non-Hodgkin's lymphoma (B-NHL), it still has some limitations because of its short half-life. Mesenchymal stromal cells (MSCs) represent an attractive approach for delivery of therapeutic agents to cancer sites owing to their tropism towards tumors, but their immunosuppression capabilities, especially induced by indoleamine 2,3-dioxygenase (IDO), should also be taken into consideration.
methodsHuman umbilical cord-derived MSCs (UC-MSCs) were genetically modified to secrete Tandab (CD3/CD19), a tetravalent bispecific tandem diabody with two binding sites for CD3 and two for CD19. The tropism of MSCs towards Raji cells in vitro was determined by migration assays, and the homing property of MSCs in vivo was analyzed with firefly luciferase-labeled MSCs (MSC-Luc) by bioluminescent imaging (BLI). The cytotoxicity of T cells induced by MSC-secreting Tandab (CD3/CD19) was detected in vitro and in vivo in combination with D-1-methyl-tryptophan (D-1MT), an IDO pathway inhibitor.
resultsThe purified Tandab (CD3/CD19) was functional with high-binding capability both for CD3-positive cells and CD19-positive cells and was able to induce specific lysis of CD19-positive cell lines (Raji, Daudi, and BJAB) in the presence of T cells. Additionally, results from co-culture killing experiments demonstrated that Tandab (CD3/CD19) secreted from MSCs was also effective. Then, we confirmed that D-1MT could enhance the cytotoxicity of T cells triggered by MSC-Tandab through reversing T cell anergy with down-regulation of CD98 and Jumonji and restoring the proliferation capacity of T cells. Furthermore, MSC-Luc could selectively migrate to tumor site in a BALB/c nude mouse model with Raji cells. And mice injected with MSC-Tandab in combination with D-1MT significantly inhibited the tumor growth.
conclusionsThese results suggest that UC-MSCs releasing Tandab (CD3/CD19) is an efficient therapeutic tool for the treatment of B cell lymphoma when combined with D-1MT.
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