ArticleBlood advances2023
Compromised antigen binding and signaling interfere with bispecific CD19 and CD79a chimeric antigen receptor function.
Article in Blood advances, 2023. 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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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 20 citations in OpenAlex.
- A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The evolving landscape of CAR T cell therapy in children and young adults with B cell acute lymphoblastic leukemia.Molecular therapy. Oncology · 2026Review
- Challenges and advances in CAR-T cell therapy for B-ALL.Biomarker research · 2026Review
- Allogeneic CD19 CAR T cells armed with an anti-rejection CD70 CAR overcome antigen escape and evade alloimmune responses.Nature communications · 2026Article
- Optimizing next-generation CAR-macrophages against solid tumors: challenges and potential strategies.Journal of hematology & oncology · 2026Review
- Article
- Cis- and trans-binding chimeric costimulatory receptors enhance T-cell fitness and tumor control.Cellular & molecular immunology · 2026Article
- Tandem CAR-T cells targeting mesothelin and MUC16 overcome tumor heterogeneity by targeting one antigen at a time.Journal for immunotherapy of cancer · 2025Article
- Utilizing genomics to identify novel immunotherapeutic targets in multiple myeloma high-risk subgroups.Genome medicine · 2025Article
- Article
- Design of sensitive monospecific and bispecific synthetic chimeric T cell receptors for cancer therapy.Nature cancer · 2025Article
- CAR-T Cell Therapy: Managing Side Effects and Overcoming Challenges.Advanced biomedical research · 2025Review
- Tandem CAR T-cells targeting CD19 and NKG2DL can overcome CD19 antigen escape in B-ALL.Frontiers in immunology · 2025Article
- From molecular design to clinical translation: dual-targeted CAR-T strategies in cancer immunotherapy.International journal of biological sciences · 2025Review
- Tandem CAR-T cell therapy: recent advances and current challenges.Frontiers in immunology · 2025Review
- Advancements and Future Directions of Dual-Target Chimeric Antigen Receptor T-Cell Therapy in Preclinical and Clinical Studies.Journal of immunology research · 2025Review
- T cell-redirecting therapies in hematological malignancies: Current developments and novel strategies for improved targeting.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Sensitive bispecific chimeric T cell receptors for cancer therapy.Research square · 2024Article
- Novel and multiple targets for chimeric antigen receptor-based therapies in lymphoma.Frontiers in oncology · 2024Review
- Chimeric antigen receptor T cells to target CD79b in B-cell lymphomas.Journal for immunotherapy of cancer · 2023Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Therapy with CD19-directed chimeric antigen receptor (CAR) T cells has transformed the treatment of advanced B-cell malignancies. However, loss of or low antigen expression can enable tumor escape and limit the duration of responses achieved with CAR T-cell therapy. Engineering bispecific CAR T cells that target 2 tumor antigens could overcome antigen-negative escape. We found that CD79a and b, which are heterodimeric components of the B-cell receptor, were expressed on 84.3% of lymphoma cases using immunohistochemistry, and 87.3% of CD79ab-positive tumors also coexpressed CD19. We generated 3 bispecific permutations: tandem, bicistronic, and pooled products of CD79a-CD19 or CD79b-CD19 CAR T cells and showed that bispecific CAR T cells prevented the outgrowth of antigen-negative cells in a CD19-loss lymphoma xenograft model. However, tandem and bicistronic CAR T cells were less effective than monospecific CD19 or CD79a CAR T cells for the treatment of tumors that only expressed CD19 or CD79, respectively. When compared with monospecific CAR T cells, T cells expressing a tandem CAR exhibited reduced binding of each target antigen, and T cells expressing a bicistronic CAR vector exhibited reduced phosphorylation of downstream CAR signaling molecules. Our study showed that despite added specificity, tandem and bicistronic CAR T cells exhibit different defects that impair recognition of tumor cells expressing a single antigen. Our data provide support for targeting multiple B-cell antigens to improve efficacy and identify areas for improvement in bispecific receptor designs.
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Registered trials
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.