Improving T Cell Receptor On-Target Specificity via Structure-Guided Design
نویسندگان
چکیده
منابع مشابه
Specific increase in T cell potency via structure-based design of a T cell receptor for adoptive immunotherapy
Adoptive immunotherapy with antigen-specific T lymphocytes is a powerful strategy for cancer treatment. However, most tumor antigens are non-reactive “self” proteins, which presents an immunotherapy design challenge. Studies have shown that tumor-specific T cell receptors (TCRs) can be transduced into normal peripheral blood lymphocytes, which persist after transfer in about 30% of patients and...
متن کاملImproving target cell specificity using a novel monovalent bispecific IgG design
Monovalent bispecific IgGs cater to a distinct set of mechanisms of action but are difficult to engineer and manufacture because of complexities associated with correct heavy and light chain pairing. We have created a novel design, "DuetMab," for efficient production of these molecules. The platform uses knobs-into-holes (KIH) technology for heterodimerization of 2 distinct heavy chains and inc...
متن کاملStructure and specificity of T cell receptor gamma/delta on major histocompatibility complex antigen-specific CD3+, CD4-, CD8- T lymphocytes
Analyses of TCR-bearing murine and human T cells have defined a unique subpopulation of T cells that express the TCR-gamma/delta proteins. The specificity of TCR-gamma/delta T cells and their role in the immune response have not yet been elucidated. Here we examine alloreactive TCR-gamma/delta T cell lines and clones that recognize MHC-encoded antigens. A BALB/c nu/nu (H-2d)-derived H-2k specif...
متن کاملSTRUCTURE AND SPECIFICITY OF T CELL RECEPTOR y/8 ON MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGEN-SPECIFIC CD3+, CD4-, CD8- T LYMPHOCYTES
Most antigen-specific peripheral murine Tlymphocytes express the Tcell differentiation antigens, CD4 or CD8, and a TCRcomposed ofa CD3-associated disulfidelinked heterodimer, TCR-a/(3 (1, 2) . However, recent studies have identified a distinct population of CD3+,CD4-,CD8cells that appear early in thymic ontogeny and are maintained in the mature thymus and the peripheral lymphoid organs througho...
متن کاملComputational Design of the Affinity and Specificity of a Therapeutic T Cell Receptor
T cell receptors (TCRs) are key to antigen-specific immunity and are increasingly being explored as therapeutics, most visibly in cancer immunotherapy. As TCRs typically possess only low-to-moderate affinity for their peptide/MHC (pMHC) ligands, there is a recognized need to develop affinity-enhanced TCR variants. Previous in vitro engineering efforts have yielded remarkable improvements in TCR...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Molecular Therapy
سال: 2019
ISSN: 1525-0016
DOI: 10.1016/j.ymthe.2018.12.010