ArticleCancer immunology research2021
A CRISPR Screen Reveals Resistance Mechanisms to CD3-Bispecific Antibody Therapy.
Article in Cancer immunology research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
17 citing papers in PubMed, 16 citations in OpenAlex.
- An In Vitro Quantitative Systems Pharmacology Platform for Characterizing CD3-Bispecific Antibody-Mediated T-Cell Activation and Tumor Cell Cytotoxicity.The AAPS journal · 2026Article
- High-throughput screening to engineer optimal T cell therapies: current knowledge and future prospects.Frontiers in oncology · 2026Review
- CD3xHER2 bsAb-Mediated Activation of Resting T-cells at HER2 Positive Tumor Clusters Is Sufficient to Trigger Bystander Eradication of Distant HER2 Negative Clusters Through IFNγ and TNFα.European journal of immunology · 2025Article
- Mechanistic insights into resistance mechanisms to T cell engagers.Frontiers in immunology · 2025Review
- Comprehensive Multi-Omics Analysis Identifies FUT1 as a Prognostic and Therapeutic Biomarker Across Pan-Cancer.International journal of medical sciences · 2025Article
- High-throughput screening for optimizing adoptive T cell therapies.Experimental hematology & oncology · 2024Review
- Nilotinib boosts the efficacy of anti-PDL1 therapy in colorectal cancer by restoring the expression of MHC-I.Journal of translational medicine · 2024Article
- Efficacy and safety of bispecific antibodies vs. immune checkpoint blockade combination therapy in cancer: a real-world comparison.Molecular cancer · 2024Review
- Precision oncology revolution: CRISPR-Cas9 and PROTAC technologies unleashed.Frontiers in genetics · 2024Review
- Advancements in cancer immunotherapies targeting CD20: from pioneering monoclonal antibodies to chimeric antigen receptor-modified T cells.Frontiers in immunology · 2024Review
- Mechanistic and pharmacodynamic studies of DuoBody-CD3x5T4 in preclinical tumor models.Life science alliance · 2022Article
- Proceedings from the Blood and Marrow Transplant Clinical Trials Network Myeloma Intergroup Workshop on Immune and Cellular Therapy in Multiple Myeloma.Transplantation and cellular therapy · 2022Article
- Tumor immunology CRISPR screening: present, past, and future.Trends in cancer · 2022Review
- CRISPR screening identifies T cell-intrinsic regulators of CD3-bispecific antibody responses.Frontiers in immunology · 2022Article
- T Cell Bispecific Antibodies: An Antibody-Based Delivery System for Inducing Antitumor Immunity.Pharmaceuticals (Basel, Switzerland) · 2021Review
- T-cell receptor-based therapy: an innovative therapeutic approach for solid tumors.Journal of hematology & oncology · 2021Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
CD3-bispecific antibodies represent an important therapeutic strategy in oncology. These molecules work by redirecting cytotoxic T cells to antigen-bearing tumor cells. Although CD3-bispecific antibodies have been developed for several clinical indications, cases of cancer-derived resistance are an emerging limitation to the more generalized application of these molecules. Here, we devised whole-genome CRISPR screens to identify cancer resistance mechanisms to CD3-bispecific antibodies across multiple targets and cancer types. By validating the screen hits, we found that deficiency in IFNγ signaling has a prominent role in cancer resistance. IFNγ functioned by stimulating the expression of T-cell killing-related molecules in a cell type-specific manner. By assessing resistance to the clinical CD3-bispecific antibody flotetuzumab, we identified core fucosylation as a critical pathway to regulate flotetuzumab binding to the CD123 antigen. Disruption of this pathway resulted in significant resistance to flotetuzumab treatment. Proper fucosylation of CD123 was required for its normal biological functions. In order to treat the resistance associated with fucosylation loss, flotetuzumab in combination with an alternative targeting CD3-bispecific antibody demonstrated superior efficacy. Together, our study reveals multiple mechanisms that can be targeted to enhance the clinical potential of current and future T-cell-engaging CD3-bispecific antibody therapies.
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What OpenQuestion holds
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.