ArticleBlood cancer journal2020
Blockade of VLA4 sensitizes leukemic and myeloma tumor cells to CD3 redirection in the bone marrow microenvironment.
Article in Blood cancer journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Targeting the immunological synapse in multiple myeloma.Discover oncology · 2026Review
- C-X-C chemokine receptor type 4 (CXCR4) antagonism in precision oncology: Clinical applications and future directions.Cancer pathogenesis and therapy · 2026Review
- From monoclonals to bispecific T cell engagers: the evolving antibody-based therapy landscape in acute myeloid leukemia.Frontiers in immunology · 2026Review
- Emerging precision medicine in multiple myeloma: clinical and preclinical landscape of T cell, natural killer cell, and macrophages engaging multi-specific antibodies.Frontiers in immunology · 2026Review
- ImmunoTar-integrative prioritization of cell surface targets for cancer immunotherapy.Bioinformatics (Oxford, England) · 2025Article
- LILRB4 on multiple myeloma cells promotes bone lesion by p-SHP2/NF-κB/RELT signal pathway.Journal of experimental & clinical cancer research : CR · 2024Article
- IMMUNOTAR - Integrative prioritization of cell surface targets for cancer immunotherapy.bioRxiv : the preprint server for biology · 2024Article
- Role of adhesion molecules in cancer and targeted therapy.Science China. Life sciences · 2024Review
- Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies.Journal of hematology & oncology · 2023Review
- First-in-human study of JNJ-63709178, a CD123/CD3 targeting antibody, in relapsed/refractory acute myeloid leukemia.Clinical and translational science · 2023Article
- Delivery of Theranostic Nanoparticles to Various Cancers by Means of Integrin-Binding Peptides.International journal of molecular sciences · 2022Review
- Natural killer cells activity against multiple myeloma cells is modulated by osteoblast-induced IL-6 and IL-10 production.Heliyon · 2022Article
- Ablation of VLA4 in multiple myeloma cells redirects tumor spread and prolongs survival.Scientific reports · 2022Article
- Therapeutics to harness the immune microenvironment in multiple myeloma.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Regulation of Malignant Myeloid Leukemia by Mesenchymal Stem Cells.Frontiers in cell and developmental biology · 2022Review
- Posttransplant blockade of CXCR4 improves leukemia complete remission rates and donor stem cell engraftment without aggravating GVHD.Cellular & molecular immunology · 2021Article
- VLA-4 Induces Chemoresistance of T Cell Acute Lymphoblastic Leukemia Cells via PYK2-Mediated Drug Efflux.Cancers · 2021Article
- Leukemia stem cell-bone marrow microenvironment interplay in acute myeloid leukemia development.Experimental hematology & oncology · 2021Review
- Overcoming the challenges associated with CD3+ T-cell redirection in cancer.British journal of cancer · 2021Review
- Insights Into Bone Marrow Niche Stability: An Adhesion and Metabolism Route.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Redirecting T cells to specifically kill malignant cells has been validated as an effective anti-cancer strategy in the clinic with the approval of blinatumomab for acute lymphoblastic leukemia. However, the immunosuppressive nature of the tumor microenvironment potentially poses a significant hurdle to T cell therapies. In hematological malignancies, the bone marrow (BM) niche is protective to leukemic stem cells and has minimized the efficacy of several anti-cancer drugs. In this study, we investigated the impact of the BM microenvironment on T cell redirection. Using bispecific antibodies targeting specific tumor antigens (CD123 and BCMA) and CD3, we observed that co-culture of acute myeloid leukemia or multiple myeloma cells with BM stromal cells protected tumor cells from bispecific antibody-T cell-mediated lysis in vitro and in vivo. Impaired CD3 redirection cytotoxicity was correlated with reduced T cell effector responses and cell-cell contact with stromal cells was implicated in reducing T cell activation and conferring protection of cancer cells. Finally, blocking the VLA4 adhesion pathway in combination with CD3 redirection reduced the stromal-mediated inhibition of cytotoxicity and T cell activation. Our results lend support to inhibiting VLA4 interactions along with administering CD3 redirection therapeutics as a novel combinatorial regimen for robust anti-cancer responses.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.