Current CD33-targeted immunotherapies typically recognize the membrane-distal V-set domain of CD33. Here, we show that decreasing the distance between T cell and leukemia cell membrane increases the ...efficacy of CD33 chimeric antigen receptor (CAR) T cells. We therefore generated and optimized second-generation CAR constructs containing single-chain variable fragments from antibodies raised against the membrane-proximal C2-set domain, which bind CD33 regardless of whether the V-set domain is present (CD33PAN antibodies). CD33PAN CAR T cells resulted in efficient tumor clearance and improved survival of immunodeficient mice bearing human AML cell xenografts and, in an AML model with limited CD33 expression, forced escape of CD33neg leukemia. Compared to CD33V-set CAR T cells, CD33PAN CAR T cells showed greater in vitro and in vivo efficacy against several human AML cell lines with differing levels of CD33 without increased expression of exhaustion markers. CD33PAN moieties were detected at a higher frequency on human leukemic stem cells, and CD33PAN CAR T cells had greater in vitro efficacy against primary human AML cells. Together, our studies demonstrate improved efficacy with CAR T cells binding CD33 close to the cell membrane, providing the rationale to investigate CD33PAN CAR T cells further toward possible clinical application.
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Fiorenza and colleagues found that decreasing the distance between T cell and leukemia cell membranes increases the efficacy of CD33 chimeric antigen receptor (CAR) T cells. CAR T cells targeting the membrane-proximal C2-set domain showed superior anti-leukemic activity, providing the rationale to investigate such cells further toward possible clinical application.
Prevention of adhesions to polypropylene mesh1 Felemovicius, Isaac; Bonsack, Margaret E; Hagerman, Gonzalo ...
Journal of the American College of Surgeons,
04/2004, Letnik:
198, Številka:
4
Journal Article
Long Distance Caregivers Watari, Kecia; Wetherell, Julie Loebach; Gatz, Margaret ...
Clinical gerontologist,
06/2006, Letnik:
29, Številka:
4
Journal Article
Recenzirano
A long distance caregiver program was developed by the Alzheimer's Association of Los Angeles to provide services to caregivers living at a distance from Los Angeles. Data on demographic ...characteristics and service use were compared between 90 long distance and 187 local caregivers. Similar to local caregiving families, the most frequently used services by long distance families included written materials, the website, and the telephone helpline. Satisfaction with services was high. Open-ended responses provided further information on unmet service needs and barriers. Results demonstrate the feasibility of a program to provide family consultation for long distance caregivers of a relative with dementia. Future work needs to focus on assisting long distance caregivers with family disagreements about care and long distance care recipients who live alone.
Many practitioners feel a growing despair over the foundations of their knowledge—over what it is they can claim to know—and how they are supposed to use this knowledge to help rather than disempower ...the people they serve. This paper argues that our accountability to the people we serve will come not from efforts to prove the authority of our knowledge, but from a more reflective and dialogic engagement with our knowledge, and with the people served through it—an engagement that seeks constantly to problematize our knowing, to probe and critique it, to trace its origins and assumptions, and explore its implications, to open it to inquiry and transformation.
This paper reviews and reflects on six papers, which describe various early home visiting interventions that resulted in positive outcomes, particularly in relation to the mother-infant relationship. ...The papers were published in a special issue of the Infant Mental Health Journal in 2006. We provide a brief overview of each paper, highlighting the conclusions drawn across the six papers. Key learning points for health visitors in the UK are explored throughout. Suggestions are described for improvements to the way in which health visiting services in the UK are structured in order to further enhance mother-infant relationships. The overall finding is that mother-infant relationships and interactions can be improved through early home visiting interventions over a period of time, and that this prevents childhood problems later on. It is recommended that specific patient groups be targeted and offered tailored programmes of interventions that have a relevant theoretical base, by trained nursing staff who are supported by an infant mental health consultant.
Systemically administered misoprostol, a PGE1 analog, has been shown to be an intestinal radioprotector. The purpose of this study was to determine if administration of misoprostol into the ...intestinal lumen can also reduce the severity of acute radiation enteritis. The rat small bowel was operatively exteriorized and segmented by means of suture ties. The remainder of the intestine and the rat were shielded in a lead box. Misoprostol was introduced into the lumen in various doses. After 30 min exposure to misoprostol, the isolated, exteriorized, segmented bowel was subjected to 11 Gy X irradiation. Five days later the animals were sacrificed and the intestines harvested for evaluation. Surviving crypt numbers per circumference and mucosal height were the criteria used for quantification of damage. Mucosa exposed to misoprostol at the time of radiation delivery showed significantly increased crypt numbers and mucosal height compared to adjacent saline-filled intestine.
Probucol is a lipid-regulating drug that also has antioxidant properties. This study was designed to test the possibility that probucol could provide radioprotection of the intestine when ...administered either intralumenally or systemically. Tissue damage was evaluated histologically by quantifying the number of crypts per circumference and the mucosal height. Animals were sacrificed 5 days after 11 Gy of X irradiation. In one series of experiments, a loop of mid small bowel was exteriorized operatively and compartmentalized into segments, each filled with probucol or saline. Intralumenal administration of probucol prior to irradiation led to a significantly greater number of crypts per circumference and mucosal height compared to saline-filled irradiated controls. In another series of experiments, five groups of rats were irradiated: (1) probucol in the small bowel lumen, (2) intravenous probucol, (3) probucol by gavage, (4) probucol added to standard rat chow and (5) saline control. In the rats given probucol intravenously prior to X irradiation, crypt numbers and mucosal height were significantly enhanced. Probucol given by gavage also resulted in protection. Rats fed a diet containing probucol showed no significant protection. Topical administration was more effective than systemic. Probucol protects the intestinal mucosa from acute radiation damage when given topically, intravenously or by gavage, but does not do so when given as a dietary supplement.
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