ArticleCancer discovery2022
Modulation of BCL-2 in Both T Cells and Tumor Cells to Enhance Chimeric Antigen Receptor T-cell Immunotherapy against Cancer.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
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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
69 citing papers in PubMed, 90 citations in OpenAlex.
- Clinical outcomes and spatial transcriptomic profiles of CD19/20 CAR-T therapy in relapsed or refractory B-cell non-Hodgkin's lymphoma.Journal for immunotherapy of cancer · 2026Trial
- TIM3-targeted delivery of venetoclax overcomes drug resistance and reinvigorates NK cell activity in acute myeloid leukemia.Nature cancer · 2026Article
- Ex vivo pretreatment with venetoclax boosts antileukemic efficacy of therapeutic γδ T cells in AML models.The Journal of clinical investigation · 2026Article
- Efficacy analysis of CAR-T cells against CD123-positive malignant tumors and exploration of the feasibility of combination therapy with venetoclax.Annals of hematology · 2026Article
- Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- A tumor-intrinsic WNT-inhibitory NOTUM program drives immune resistance in microsatellite stable colorectal cancer.Cell reports. Medicine · 2026Article
- Targeting CD74 may mitigate immune-escape features and enhance BCMA CAR-T activity in preclinical models of relapsed/refractory multiple myeloma.Journal for immunotherapy of cancer · 2026Article
- Therapeutic targeting of BCL-2 during CART cell production augments potency through non-apoptotic adaptive changes.Signal transduction and targeted therapy · 2026Article
- Combining Small-Molecular Compounds With CAR T-Cell Therapy: Novel Strategies for Enhanced Cancer Immunotherapy.Cancer innovation · 2026Review
- Current evidence and strategies for bridging therapy in CD19-directed chimeric antigen receptor T-cell therapy for relapsed/refractory large B-cell lymphomas.Annals of hematology · 2026Review
- Synthetic lethality of MCL-1 inhibition and CAR-T therapy in aggressive B-cell lymphoma.Leukemia · 2026Article
- IL-5 CAR-T cell therapy induces effective remission in hypereosinophilic disorders.Journal of hematology & oncology · 2026Article
- Protein Post-Translational Modifications in the Regulation of Ferroptosis: New Opportunities and Challenges for Cancer Immunotherapy.International journal of biological sciences · 2026Review
- Potential of small-molecule targeted drugs in combination with CAR-T cell therapy for hematologic lymphomas.Frontiers in immunology · 2026Review
- Functional differences between CLL- and ALL-derived CAR T cells in a 3D tumor microenvironment highlight CXCR4 and IL-10 as potential modulatory targets.HemaSphere · 2025Article
- DLBCL Cells Emerge after CD19 CAR T Cells with Cross-Antigen Resistance and a Gene Signature Predictive of Clinical CAR T-cell Response.Blood cancer discovery · 2025Article
- Predictors of response to CD19 chimeric antigen receptor T-cell therapy in large B-cell lymphoma: a consolidated review.Current opinion in oncology · 2025Review
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- Limitations of CAR-T-Cell Therapy in Hematologic Malignancies: Focusing on Antigen Escape and T-Cell Dysfunction.International journal of molecular sciences · 2025Review
- Mechanisms of Resistance to CAR T-Cells and How to Overcome Them.Methods and protocols · 2025Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
29 authors at 3 institutions in 2 countries.
Funding
Abstract
Chimeric antigen receptor T-cell (CART) immunotherapy led to unprecedented responses in patients with refractory/relapsed B-cell non-Hodgkin lymphoma (NHL); nevertheless, two thirds of patients experience treatment failure. Resistance to apoptosis is a key feature of cancer cells, and it is associated with treatment failure. In 87 patients with NHL treated with anti-CD19 CART, we found that chromosomal alteration of B-cell lymphoma 2 (BCL-2), a critical antiapoptotic regulator, in lymphoma cells was associated with reduced survival. Therefore, we combined CART19 with the FDA-approved BCL-2 inhibitor venetoclax and demonstrated in vivo synergy in venetoclax-sensitive NHL. However, higher venetoclax doses needed for venetoclax-resistant lymphomas resulted in CART toxicity. To overcome this limitation, we developed venetoclax-resistant CART by overexpressing mutated BCL-2(F104L), which is not recognized by venetoclax. Notably, BCL-2(F104L)-CART19 synergized with venetoclax in multiple lymphoma xenograft models. Furthermore, we uncovered that BCL-2 overexpression in T cells intrinsically enhanced CART antitumor activity in preclinical models and in patients by prolonging CART persistence. SIGNIFICANCE: This study highlights the role of BCL-2 in resistance to CART immunotherapy for cancer and introduces a novel concept for combination therapies-the engineering of CART cells to make them resistant to proapoptotic small molecules, thereby enhancing the therapeutic index of these combination therapies. This article is highlighted in the In This Issue feature, p. 2221.
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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.