Preclinical studies show that Co-STARs combine the advantages of chimeric antigen and T cell receptors for the treatment of tumors with low antigen densities.

التفاصيل البيبلوغرافية
العنوان:	Preclinical studies show that Co-STARs combine the advantages of chimeric antigen and T cell receptors for the treatment of tumors with low antigen densities.
المؤلفون:	Mog BJ; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA., Marcou N; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., DiNapoli SR; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Pearlman AH; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Nichakawade TD; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.; Institute for NanoBioTechnology, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA., Hwang MS; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Douglass J; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Hsiue EH; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Glavaris S; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Wright KM; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA., Konig MF; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA., Paul S; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Wyhs N; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Ge J; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Miller MS; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA., Azurmendi P; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA., Watson E; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Pardoll DM; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA., Gabelli SB; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA.; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Bettegowda C; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Papadopoulos N; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Kinzler KW; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA., Vogelstein B; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Zhou S; Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Lustgarten Pancreatic Cancer Research Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA.
المصدر:	Science translational medicine [Sci Transl Med] 2024 Jul 10; Vol. 16 (755), pp. eadg7123. Date of Electronic Publication: 2024 Jul 10.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101505086 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1946-6242 (Electronic) Linking ISSN: 19466234 NLM ISO Abbreviation: Sci Transl Med Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Washington, DC : American Association for the Advancement of Science
مواضيع طبية MeSH:	Receptors, Chimeric Antigen/metabolism , Receptors, Chimeric Antigen/immunology , Receptors, Antigen, T-Cell/metabolism , Receptors, Antigen, T-Cell/immunology , Neoplasms/immunology , Neoplasms/therapy, Humans ; Animals ; Mice ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Cell Line, Tumor ; Antigens, Neoplasm/immunology ; Antigens, Neoplasm/metabolism ; Signal Transduction
مستخلص:	Two types of engineered T cells have been successfully used to treat patients with cancer, one with an antigen recognition domain derived from antibodies [chimeric antigen receptors (CARs)] and the other derived from T cell receptors (TCRs). CARs use high-affinity antigen-binding domains and costimulatory domains to induce T cell activation but can only react against target cells with relatively high amounts of antigen. TCRs have a much lower affinity for their antigens but can react against target cells displaying only a few antigen molecules. Here, we describe a new type of receptor, called a Co-STAR (for costimulatory synthetic TCR and antigen receptor), that combines aspects of both CARs and TCRs. In Co-STARs, the antigen-recognizing components of TCRs are replaced by high-affinity antibody fragments, and costimulation is provided by two modules that drive NF-κB signaling (MyD88 and CD40). Using a TCR-mimic antibody fragment that targets a recurrent p53 neoantigen presented in a common human leukocyte antigen (HLA) allele, we demonstrate that T cells equipped with Co-STARs can kill cancer cells bearing low densities of antigen better than T cells engineered with conventional CARs and patient-derived TCRs in vitro. In mouse models, we show that Co-STARs mediate more robust T cell expansion and more durable tumor regressions than TCRs similarly modified with MyD88 and CD40 costimulation. Our data suggest that Co-STARs may have utility for other peptide-HLA antigens in cancer and other targets where antigen density may limit the efficacy of engineered T cells.
معلومات مُعتمدة:	K08 CA270403 United States CA NCI NIH HHS
المشرفين على المادة:	0 (Receptors, Chimeric Antigen) 0 (Receptors, Antigen, T-Cell) 0 (Antigens, Neoplasm)
تواريخ الأحداث:	Date Created: 20240710 Date Completed: 20240710 Latest Revision: 20240925
رمز التحديث:	20240925
DOI:	10.1126/scitranslmed.adg7123
PMID:	38985855
قاعدة البيانات:	MEDLINE

الوصف
تدمد:	1946-6242
DOI:	10.1126/scitranslmed.adg7123