Matches in SemOpenAlex for { <https://semopenalex.org/work/W2904392624> ?p ?o ?g. }
- W2904392624 endingPage "2075" @default.
- W2904392624 startingPage "2061" @default.
- W2904392624 abstract "Patients with hepatocellular carcinoma (HCC) have a poor prognosis and limited therapeutic options. Alpha‐fetoprotein (AFP) is often expressed at high levels in HCC and is an established clinical biomarker of the disease. Expression of AFP in nonmalignant liver can occur, particularly in a subset of progenitor cells and during chronic inflammation, at levels typically lower than in HCC. This cancer‐specific overexpression indicates that AFP may be a promising target for immunotherapy. We verified expression of AFP in normal and diseased tissue and generated an affinity‐optimized T‐cell receptor (TCR) with specificity to AFP/HLA‐A*02 + tumors. Expression of AFP was investigated using database searches, by qPCR, and by immunohistochemistry (IHC) analysis of a panel of human tissue samples, including normal, diseased, and malignant liver. Using in vitro mutagenesis and screening, we generated a TCR that recognizes the HLA‐A*02‐restricted AFP 158‐166 peptide, FMNKFIYEI, with an optimum balance of potency and specificity. These properties were confirmed by an extension of the alanine scan (X‐scan) and testing TCR‐transduced T cells against normal and tumor cells covering a variety of tissues, cell types, and human leukocyte antigen (HLA) alleles. Conclusion: We have used a combination of physicochemical, in silico , and cell biology methods for optimizing a TCR for improved affinity and function, with properties that are expected to allow TCR‐transduced T cells to differentiate between antigen levels on nonmalignant and cancer cells. T cells transduced with this TCR constitute the basis for a trial of HCC adoptive T‐cell immunotherapy." @default.
- W2904392624 created "2018-12-22" @default.
- W2904392624 creator A5007182693 @default.
- W2904392624 creator A5009322753 @default.
- W2904392624 creator A5009496778 @default.
- W2904392624 creator A5018440196 @default.
- W2904392624 creator A5024743571 @default.
- W2904392624 creator A5024914425 @default.
- W2904392624 creator A5042255336 @default.
- W2904392624 creator A5046364897 @default.
- W2904392624 creator A5057687806 @default.
- W2904392624 creator A5064588365 @default.
- W2904392624 creator A5069617414 @default.
- W2904392624 creator A5070777703 @default.
- W2904392624 creator A5073275745 @default.
- W2904392624 creator A5077936678 @default.
- W2904392624 creator A5089902367 @default.
- W2904392624 date "2019-02-14" @default.
- W2904392624 modified "2023-10-03" @default.
- W2904392624 title "Tuning T‐Cell Receptor Affinity to Optimize Clinical Risk‐Benefit When Targeting Alpha‐Fetoprotein–Positive Liver Cancer" @default.
- W2904392624 cites W1519645049 @default.
- W2904392624 cites W1594353637 @default.
- W2904392624 cites W1719275795 @default.
- W2904392624 cites W1757407923 @default.
- W2904392624 cites W1771948246 @default.
- W2904392624 cites W1821172549 @default.
- W2904392624 cites W1839209630 @default.
- W2904392624 cites W1877911682 @default.
- W2904392624 cites W1964211639 @default.
- W2904392624 cites W1977917700 @default.
- W2904392624 cites W1983143892 @default.
- W2904392624 cites W1984817631 @default.
- W2904392624 cites W1988684186 @default.
- W2904392624 cites W1991420086 @default.
- W2904392624 cites W1994736606 @default.
- W2904392624 cites W2002422546 @default.
- W2904392624 cites W2007605965 @default.
- W2904392624 cites W2043636285 @default.
- W2904392624 cites W2049010867 @default.
- W2904392624 cites W2050302632 @default.
- W2904392624 cites W2056873861 @default.
- W2904392624 cites W2061764944 @default.
- W2904392624 cites W2070748533 @default.
- W2904392624 cites W2079909044 @default.
- W2904392624 cites W2094945699 @default.
- W2904392624 cites W2128377922 @default.
- W2904392624 cites W2139681481 @default.
- W2904392624 cites W2143626441 @default.
- W2904392624 cites W2147771351 @default.
- W2904392624 cites W2165119413 @default.
- W2904392624 cites W2170845559 @default.
- W2904392624 cites W2177830250 @default.
- W2904392624 cites W2342127666 @default.
- W2904392624 cites W2345873391 @default.
- W2904392624 cites W2522695119 @default.
- W2904392624 cites W2528356436 @default.
- W2904392624 cites W2533389133 @default.
- W2904392624 cites W2560186031 @default.
- W2904392624 cites W2586634548 @default.
- W2904392624 cites W2611873621 @default.
- W2904392624 cites W2742087584 @default.
- W2904392624 cites W2748034335 @default.
- W2904392624 cites W2790734406 @default.
- W2904392624 cites W2793199674 @default.
- W2904392624 cites W2901331779 @default.
- W2904392624 doi "https://doi.org/10.1002/hep.30477" @default.
- W2904392624 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6593660" @default.
- W2904392624 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30561769" @default.
- W2904392624 hasPublicationYear "2019" @default.
- W2904392624 type Work @default.
- W2904392624 sameAs 2904392624 @default.
- W2904392624 citedByCount "37" @default.
- W2904392624 countsByYear W29043926242019 @default.
- W2904392624 countsByYear W29043926242020 @default.
- W2904392624 countsByYear W29043926242021 @default.
- W2904392624 countsByYear W29043926242022 @default.
- W2904392624 countsByYear W29043926242023 @default.
- W2904392624 crossrefType "journal-article" @default.
- W2904392624 hasAuthorship W2904392624A5007182693 @default.
- W2904392624 hasAuthorship W2904392624A5009322753 @default.
- W2904392624 hasAuthorship W2904392624A5009496778 @default.
- W2904392624 hasAuthorship W2904392624A5018440196 @default.
- W2904392624 hasAuthorship W2904392624A5024743571 @default.
- W2904392624 hasAuthorship W2904392624A5024914425 @default.
- W2904392624 hasAuthorship W2904392624A5042255336 @default.
- W2904392624 hasAuthorship W2904392624A5046364897 @default.
- W2904392624 hasAuthorship W2904392624A5057687806 @default.
- W2904392624 hasAuthorship W2904392624A5064588365 @default.
- W2904392624 hasAuthorship W2904392624A5069617414 @default.
- W2904392624 hasAuthorship W2904392624A5070777703 @default.
- W2904392624 hasAuthorship W2904392624A5073275745 @default.
- W2904392624 hasAuthorship W2904392624A5077936678 @default.
- W2904392624 hasAuthorship W2904392624A5089902367 @default.
- W2904392624 hasBestOaLocation W29043926241 @default.
- W2904392624 hasConcept C121608353 @default.
- W2904392624 hasConcept C126322002 @default.
- W2904392624 hasConcept C147483822 @default.
- W2904392624 hasConcept C19317047 @default.