ArticleClinical cancer research : an official journal of the American Association for Cancer Research2009
Characterization of genetically modified T-cell receptors that recognize the CEA:691-699 peptide in the context of HLA-A2.1 on human colorectal cancer cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 119 citations in OpenAlex.
- Targeting Carcinoembryonic Antigen with DNA Vaccination: On-Target Adverse Events Link with Immunologic and Clinical Outcomes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Trial
- Development of human anti-murine T-cell receptor antibodies in both responding and nonresponding patients enrolled in TCR gene therapy trials.Clinical cancer research : an official journal of the American Association for Cancer Research · 2010Trial
- Trial
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- Identification of neoepitope reactive T-cell receptors guided by HLA-A*03:01 and HLA-A*11:01 immunopeptidomics.Journal for immunotherapy of cancer · 2023Article
- Advancing cell-based cancer immunotherapy through stem cell engineering.Cell stem cell · 2023Review
- Cell Therapy as Target Therapy against Colon Cancer Stem Cells.International journal of molecular sciences · 2023Review
- Dynamics and specificities of T cells in cancer immunotherapy.Nature reviews. Cancer · 2023Review
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- Signaling via a CD28/CD40 chimeric costimulatory antigen receptor (CoStAR™), targeting folate receptor alpha, enhances T cell activity and augments tumor reactivity of tumor infiltrating lymphocytes.Frontiers in immunology · 2023Article
- Recruiting Immunity for the Fight against Colorectal Cancer: Current Status and Challenges.International journal of molecular sciences · 2022Review
- Validation and promise of a TCR mimic antibody for cancer immunotherapy of hepatocellular carcinoma.Scientific reports · 2022Article
- Review
- Chemical augmentation of mitochondrial electron transport chains tunes T cell activation threshold in tumors.Journal for immunotherapy of cancer · 2022Article
- When Onco-Immunotherapy Meets Cold Atmospheric Plasma: Implications on CAR-T Therapies.Frontiers in oncology · 2022Review
- Cell Therapy for Colorectal Cancer: The Promise of Chimeric Antigen Receptor (CAR)-T Cells.International journal of molecular sciences · 2021Review
- Review
- MHC Class I Deficiency in Solid Tumors and Therapeutic Strategies to Overcome It.International journal of molecular sciences · 2021Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeCarcinoembryonic antigen (CEA) is a tumor-associated protein expressed on a variety of adenocarcinomas. To develop an immunotherapy for patients with cancers that overexpress CEA, we isolated and genetically modified a T-cell receptors (TCRs) that specifically bound a CEA peptide on human cancer cells. EXPERIMENTAL
designHLA-A2.1 transgenic mice were immunized with CEA:691-699. A CEA-reactive TCR was isolated from splenocytes of these mice and was genetically introduced into human peripheral blood lymphocytes via RNA electroporation or retroviral transduction. Amino acid substitutions were introduced throughout the complementarity determining regions (CDR1, CDR2, and CDR3) of both TCR alpha and beta chains to improve recognition of CEA.
resultsMurine lymphocytes bearing the CEA-reactive TCR specifically recognized peptide-loaded T2 cells and HLA-A2.1(+) CEA(+) human colon cancer cells. Both CD8(+) and CD4(+) human lymphocytes expressing the murine TCR specifically recognized peptide-loaded T2 cells. However, only gene-modified CD8(+) lymphocytes specifically recognized HLA-A2.1(+) CEA(+) colon cancer cell lines, and tumor cell recognition was weak and variable. We identified two substitutions in the CDR3 of the alpha chain that significantly influenced tumor cell recognition by human peripheral blood lymphocytes. One substitution, T for S at position 112 (S112T), enhanced tumor cell recognition by CD8(+) lymphocytes, and a second dually substituted receptor (S112T L110F) enhanced tumor cell recognition by CD4(+) T cells.
conclusionsThe modified CEA-reactive TCRs are good candidates for future gene therapy clinical trials and show the power of selected amino acid substitutions in the antigen-binding regions of the TCR to enhance desired reactivities.
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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.