ELIZA cgi-bash version rev. 1.91
- Medical English LInking keywords finder for the PubMed Zipped Archive (ELIZA) -

return kwic search for function out of >500 occurrences
288503 occurrences (No.86 in the rank) during 5 years in the PubMed. [cache]
174) Our findings both suggest that tonic 4-1BB-based signaling is beneficial to CAR function and demonstrate the utility of bedside-to-bench-to-bedside translation in the design and implementation of CAR T cell therapies.
--- ABSTRACT ---
PMID:33888899 DOI:10.1038/s41591-021-01326-5
2021 Nature medicine
* Antigen-independent activation enhances the efficacy of 4-1BB-costimulated CD22 CAR T cells.
- While CD19-directed chimeric antigen receptor (CAR) T cells can induce remission in patients with B cell acute lymphoblastic leukemia (ALL), a large subset relapse with CD19- disease. Like CD19, CD22 is broadly expressed by B-lineage cells and thus serves as an alternative immunotherapy target in ALL. Here we present the composite outcomes of two pilot clinical trials ( NCT02588456 and NCT02650414 ) of T cells bearing a 4-1BB-based, CD22-targeting CAR in patients with relapsed or refractory ALL. The primary end point of these studies was to assess safety, and the secondary end point was antileukemic efficacy. We observed unexpectedly low response rates, prompting us to perform detailed interrogation of the responsible CAR biology. We found that shortening of the amino acid linker connecting the variable heavy and light chains of the CAR antigen-binding domain drove receptor homodimerization and antigen-independent signaling. In contrast to CD28-based CARs, autonomously signaling 4-1BB-based CARs demonstrated enhanced immune synapse formation, activation of pro-inflammatory genes and superior effector function. We validated this association between autonomous signaling and enhanced function in several CAR constructs and, on the basis of these observations, designed a new short-linker CD22 single-chain variable fragment for clinical evaluation. Our findings both suggest that tonic 4-1BB-based signaling is beneficial to CAR function and demonstrate the utility of bedside-to-bench-to-bedside translation in the design and implementation of CAR T cell therapies.
--- ABSTRACT END ---
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(1)86 *null* (9)5 following (17)3 mutations (25)2 for
(2)72 of (10)5 was (18)3 not (26)2 have
(3)68 and (11)5 with (19)3 were (27)2 including
(4)63 in (12)4 by (20)3 which (28)2 measures
(5)16 is (13)4 has (21)2 after (29)2 or
(6)13 as (14)4 tests (22)2 among (30)2 quality
(7)5 are (15)4 to (23)2 data (31)2 that
(8)5 associated (16)3 at (24)2 during (32)2 variants

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--- WordNet output for function --- =>1.機能, 関数, 役割, 働き, 2.機能する, 作用する, 働く, 役目を果たす, 3.社交的会合, パーティー, 儀式 Overview of noun function The noun function has 7 senses (first 3 from tagged texts) 1. (43) function, mathematical function, single-valued function, map, mapping -- ((mathematics) a mathematical relation such that each element of a given set (the domain of the function) is associated with an element of another set (the range of the function)) 2. (24) function, purpose, role, use -- (what something is used for; "the function of an auger is to bore holes"; "ballet is beautiful but what use is it?") 3. (7) function, office, part, role -- (the actions and activities assigned to or required or expected of a person or group; "the function of a teacher"; "the government must do its part"; "play its role") 4. function -- (a relation such that one thing is dependent on another; "height is a function of age"; "price is a function of supply and demand") 5. function -- (a formal or official social gathering or ceremony; "it was a black-tie function") 6. affair, occasion, social occasion, function, social function -- (a vaguely specified social event; "the party was quite an affair"; "an occasion arranged to honor the president"; "a seemingly endless round of social functions") 7. routine, subroutine, subprogram, procedure, function -- (a set sequence of steps, part of larger computer program) Overview of verb function The verb function has 3 senses (first 3 from tagged texts) 1. (9) function, work, operate, go, run -- (perform as expected when applied; "The washing machine won't go unless it's plugged in"; "Does this old car still run well?"; "This old radio doesn't work anymore") 2. (3) serve, function -- (serve a purpose, role, or function; "The tree stump serves as a table"; "The female students served as a control group"; "This table would serve very well"; "His freedom served him well"; "The table functions as a desk") 3. (1) officiate, function -- (perform duties attached to a particular office or place or function; "His wife officiated as his private secretary") --- WordNet end ---