Overcoming Target Driven Fratricide for T Cell Therapy
نویسندگان
چکیده
منابع مشابه
Overcoming Antigen Escape with CAR T-cell Therapy.
Sotillo and colleagues describe the molecular events associated with apparent loss of target antigen expression following CAR T-cell therapy. We propose that broader immune activation is required to prevent outgrowth of tumor antigen escape variants following targeted therapies.
متن کاملNK-cell fratricide
The intercellular transfer of plasma membrane patches, also known as trogocytosis, has a strong impact on the function and fate of immune cells. We have recently shown that natural killer (NK) cells undergo fratricide following the trogocytosis-mediated acquisition of tumor-derived NKG2D ligands. Malignant cells may therefore employ trogocytosis to escape NKG2D-mediated immune responses.
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2B4 (CD244) and its ligand, CD48, are expressed on all natural killer (NK) cells. In studies using 2B4-deficient, CD48-deficient, or wild-type NK cells with blocking antibodies, we found that in the absence of 2B4-CD48 interactions, activated murine NK cells kill each other. We also show that NK-NK fratricide in the absence of 2B4-CD48 interaction is dependent on perforin both in vitro and in v...
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The clinical use of lymphocytes engineered to express high affinity T-cell receptors (TCRs) specific for two broadly expressed tumor-associated antigens is strongly limited by MHC-restricted fratricide of lymphocytes and TCR-mediated killing of hematopoietic stem cells. Specific clinical applications must therefore be conceived to bypass these limitations.
متن کاملChimeric antigen receptor T-cell therapy to target hematologic malignancies.
Several decades of humoral immunotherapy using monoclonal antibodies and cellular immunotherapy using hematopoietic cell transplantation have recently culminated in a successful merger: the development and clinical application of genetically engineered antibody-T cell chimeras. Also known as chimeric antigen receptor T cells (CAR T cells), these entities combine the exquisite antigen specificit...
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ژورنال
عنوان ژورنال: Frontiers in Immunology
سال: 2018
ISSN: 1664-3224
DOI: 10.3389/fimmu.2018.02940