ArticlemAbs2014
CEA/CD3 bispecific antibody MEDI-565/AMG 211 activation of T cells and subsequent killing of human tumors is independent of mutations commonly found in colorectal adenocarcinomas.
Article in mAbs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 89 citations in OpenAlex.
- Advances in Bispecific Antibodies and Antibody-Drug Conjugates for Colorectal Cancer Treatment.Antibodies (Basel, Switzerland) · 2026Review
- A New Paradigm of Bispecific Antibodies in Clinical Management of Gastrointestinal Cancers.Oncology research · 2026Review
- An Overview on T-Cell Engagers: The Current Position in Both the Biological and Mathematical Context.Computational and structural biotechnology journal · 2026Review
- CEA-4-1BBL: CEACAM5-Targeted 4-1BB Ligand Fusion Proteins for Cis Co-Stimulation with CEA-TCB.Antibodies (Basel, Switzerland) · 2025Article
- Development of a novel anti-CEACAM5 VHH for SPECT imaging and potential cancer therapy applications.European journal of nuclear medicine and molecular imaging · 2025Article
- Fragment-Based Immune Cell Engager Antibodies in Treatment of Cancer, Infectious and Autoimmune Diseases: Lessons and Insights from Clinical and Translational Studies.Antibodies (Basel, Switzerland) · 2025Review
- Clinical Progresses and Challenges of Bispecific Antibodies for the Treatment of Solid Tumors.Molecular diagnosis & therapy · 2024Review
- Hyperthermia in Combination with Emerging Targeted and Immunotherapies as a New Approach in Cancer Treatment.Cancers · 2024Review
- Targeting CEACAM5-positive solid tumors using NILK-2401, a novel CEACAM5xCD47 κλ bispecific antibody.Frontiers in immunology · 2024Article
- Development and characterization of NILK-2301, a novel CEACAM5xCD3 κλ bispecific antibody for immunotherapy of CEACAM5-expressing cancers.Journal of hematology & oncology · 2023Article
- Bispecific Antibodies in Lung Cancer: A State-of-the-Art Review.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Immuno-PET of colorectal cancer with a CEA-targeted [68 Ga]Ga-nanobody: from bench to bedside.European journal of nuclear medicine and molecular imaging · 2023Article
- Improved Tumor Responses with Sequential Targeted α-Particles Followed by Interleukin 2 Immunocytokine Therapies in Treatment of CEA-Positive Breast and Colon Tumors in CEA Transgenic Mice.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022Article
- Recruiting Immunity for the Fight against Colorectal Cancer: Current Status and Challenges.International journal of molecular sciences · 2022Review
- Characterization of a novel bispecific antibody targeting tissue factor-positive tumors with T cell engagement.Acta pharmaceutica Sinica. B · 2022Article
- T-cell surface generation of dual bivalent, bispecific T-cell engaging, RNA duplex cross-linked antibodies (dbBiTERs) for re-directed tumor cell lysis.Biotechnology journal · 2022Article
- Oncolytic virus driven T-cell-based combination immunotherapy platform for colorectal cancer.Frontiers in immunology · 2022Article
- Recent advances and challenges of bispecific antibodies in solid tumors.Experimental hematology & oncology · 2021Review
- Structural design of tetravalent T-cell engaging bispecific antibodies: improve developability by engineering disulfide bonds.Journal of biological engineering · 2021Article
- Generation of fully human anti-GPC3 antibodies with high-affinity recognition of GPC3 positive tumors.Investigational new drugs · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Individual or combinations of somatic mutations found in genes from colorectal cancers can redirect the effects of chemotherapy and targeted agents on cancer cell survival and, consequently, on clinical outcome. Novel therapeutics with mechanisms of action that are independent of mutational status would therefore fulfill a current unmet clinical need. Here the CEA and CD3 bispecific single-chain antibody MEDI-565 (also known as MT111 and AMG 211) was evaluated for its ability to activate T cells both in vitro and in vivo and to kill human tumor cell lines harboring various somatic mutations commonly found in colorectal cancers. MEDI-565 specifically bound to normal and malignant tissues in a CEA-specific manner, and only killed CEA positive cells. The BiTE® antibody construct mediated T cell-directed killing of CEA positive tumor cells within 6 hours, at low effector-to-target ratios which were independent of high concentrations of soluble CEA. The potency of in vitro lysis was dependent on CEA antigen density but independent of the mutational status in cancer cell lines. Importantly, individual or combinations of mutated KRAS and BRAF oncogenes, activating PI3KCA mutations, loss of PTEN expression, and loss-of-function mutations in TP53 did not reduce the activity in vitro. MEDI-565 also prevented growth of human xenograft tumors which harbored various mutations. These findings suggest that MEDI-565 represents a potential treatment option for patients with CEA positive tumors of diverse origin, including those with individual or combinations of somatic mutations that may be less responsive to chemotherapy and other targeted agents.
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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.