FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2037337367> ?p ?o ?g. }

• W2037337367 endingPage "1745" @default.
• W2037337367 startingPage "1744" @default.
• W2037337367 abstract "A recent article by Bendle et al.1Bendle GM Linnemann C Hooijkaas AI Bies L de Witte MA Jorritsma A et al.Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy.Nat Med. 2010; 16: 565-570Crossref PubMed Scopus (329) Google Scholar reported a high incidence of lethal graft-versus-host disease (GVHD) in mice receiving a lymphodepleting regimen followed by syngeneic cells transduced with genes encoding T-cell receptors (TCRs). The GVHD was manifested as cachexia, anemia, loss of hematopoietic reconstitution, pancreatitis, colitis, and death. A recent in vitro study by van Loenen et al. suggested that introduction of new TCRs into human lymphocytes could lead to the generation of mixed-TCR dimers with alloreactivity, although no in vivo data were presented.2van Loenen MM de Boer R Amir AL Hagedoorn RS Volbeda GL Willemze R et al.Mixed T cell receptor dimers harbor potentially harmful neoreactivity.Proc Natl Acad Sci U S A. 2010; 107: 10972-10977Crossref PubMed Scopus (169) Google Scholar We have treated 106 patients in the Surgery Branch of the National Cancer Institute with autologous T cells transduced with seven different gammaretroviral vectors encoding antitumor TCRs (Table 1; refs. 3Morgan RA Dudley ME Wunderlich JR Hughes MS Yang JC Sherry RM et al.Cancer regression in patients after transfer of genetically engineered lymphocytes.Science. 2006; 314: 126-129Crossref PubMed Scopus (2122) Google Scholar and 4Johnson LA Morgan RA Dudley ME Cassard L Yang JC Hughes MS et al.Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen.Blood. 2009; 114: 535-546Crossref PubMed Scopus (1093) Google Scholar and unpublished observations) and have seen no evidence of GVHD in any patient. Each of these patients received a lymphodepleting regimen of 60 mg/kg of cyclophosphamide for 2 days followed by 5 days of fludarabine at 25 mg/m2. The TCRs were of human origin in 77 patients and of mouse origin in 29 patients. In addition, we treated 6 patients who received the same cyclophosphamide-fludarabine regimen plus 600 cGy whole-body irradiation and TCR-transduced cells, and none of these patients showed any evidence of GVHD. An additional 44 patients were treated with these TCR-transduced cells without the lymphodepleting regimen, and none developed GVHD. The transduced TCRs in all of these studies manifested potent activity based on in vitro assays and the ability of transferred cells to mediate tumor regression in some patients.Table 1Patients receiving autologous T-cell receptor-transduced peripheral blood lymphocytes or autologous tumor-infiltrating lymphocytes after the same lymphodepleting regimenTCR-transduced PBLsSource of receptorVector constructaRegulatory elements facilitating expression of the TCR β-chain: PGK, promoter from human phosphoglycerate kinase gene; IRES, internal ribosome entry site from human poliovirus; T2A, ribosomal skip peptide from Thosea asigna virus; P2A, ribosomal skip peptide from porcine teschovirus 1.No. of patientsAnti-gp100:209-217HumanPGK10Anti-MART-1:27-35(F4)HumanIRES27Anti-MART-1:27-35(F5)HumanT2A21Anti-NY-ESO-1:157-165HumanP2A19Anti-CEA:691-699MouseP2A3Anti-p53:264-272MouseIRES11Anti-gp100:154-162MouseIRES15Total no. of patients106PBL, peripheral blood lymphocyte; TCR, T-cell receptor.a Regulatory elements facilitating expression of the TCR β-chain: PGK, promoter from human phosphoglycerate kinase gene; IRES, internal ribosome entry site from human poliovirus; T2A, ribosomal skip peptide from Thosea asigna virus; P2A, ribosomal skip peptide from porcine teschovirus 1. Open table in a new tab PBL, peripheral blood lymphocyte; TCR, T-cell receptor. We compared the clinical course of patients who received TCR-transduced cells with 115 patients treated by us who received the adoptive transfer of autologous nontransduced tumor-infiltrating lymphocytes following the same nonmyeloablative chemotherapy regimen.5Dudley ME Yang JC Sherry R Hughes MS Royal R Kammula U et al.Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens.J Clin Oncol. 2008; 26: 5233-5239Crossref PubMed Scopus (1091) Google Scholar,6Rosenberg SA Dudley ME Adoptive cell therapy for the treatment of patients with metastatic melanoma.Curr Opin Immunol. 2009; 21: 233-240Crossref PubMed Scopus (491) Google Scholar As shown in Table 2, there were no meaningful differences in clinical parameters between the two groups, including the number of days to recovery of absolute neutrophil count to 500 cells/mm3, absolute lymphocyte count to 1,000 cells/mm3, or platelets to 30,000 cells/mm3. In addition, there was no difference from start of treatment to discharge from the hospital, in weight loss or maximum liver function tests such as bilirubin. No patient in either group developed pancreatitis or prolonged colitis. There were no treatment-related deaths in any of the 106 patients who received TCR-transduced peripheral blood lymphocytes (PBLs).Table 2Analysis of 103 patients who received T-cell receptor-transduced peripheral blood lymphocytes compared with 115 patients who received tumor-infiltrating lymphocytesLaboratory valueHuman TCRsMouse TCRsTILsANC >500 cells/mm3 (days)Median13.014.014.0Mean ± s.e.m.13.6 ± 0.414.7 ± 0.514.1 ± 0.3ALC >1,000 cells/mm3 (days)Median151914Mean ± s.e.m.18.1 ± 1.519.3 ± 1.415.8 ± 0.9Platelets >30,000 cells/mm3 (days)Median9.08.59.0Mean ± s.e.m.11.0 ± 0.79.3 ± 0.610.2 ± 0.3Start to discharge (days)Median212520Mean ± s.e.m.24.2 ± 1.627.2 ± 1.522.2 ± 0.6Maximum weight loss (kg)Median3.65.83.7Mean ± s.e.m.4.7 ± 0.55.8 ± 0.64.4 ± 0.3Maximum bilirubin (mg/dl)Median1.61.71.4Mean ± s.e.m.2.0 ± 0.22.7 ± 0.61.9 ± 0.2ALC, absolute lymphocyte count; ANC, absolute neutrophil count; TCR, T-cell receptor; TIL, tumor-infiltrating lymphocyte. Open table in a new tab ALC, absolute lymphocyte count; ANC, absolute neutrophil count; TCR, T-cell receptor; TIL, tumor-infiltrating lymphocyte. It thus appears that in contrast to the report of mouse models by Bendle et al., humans receiving autologous T cells transduced with human or mouse TCRs did not develop evidence of GVHD. How then do we reconcile these divergent data? Bendle et al. claimed that a reduced level of GVHD occurs with transfer of transduced monoclonal compared with polyclonal populations; however, all our patients received polyclonal populations of transduced PBLs. To obtain the large number of cells needed to treat patients, human cells were often cultured for approximately 1 month as compared with only a few days of culture of mouse cells. However, 25 of the 106 patients received anti-TCR transduced cells cultured for only 4–8 days. In the human trials interleukin-2 administration was begun on the day of cell infusion as compared with 10 days after cell infusion in the mouse. Bendle et al. also reported a lower level of GVHD using an internal ribosomal entry site sequence rather than a 2A ribosomal skip sequence to link the TCR α- and β-chains, although we saw no GVHD using either construct nor the use of a PGK internal promoter (Table 1). Our clinical trials in patients with metastatic cancer refractory to standard treatments have resulted in objective cancer regressions using autologous cells transduced with the anti-MART-1:27-35, the anti-gp100:154-162 (refs. 2van Loenen MM de Boer R Amir AL Hagedoorn RS Volbeda GL Willemze R et al.Mixed T cell receptor dimers harbor potentially harmful neoreactivity.Proc Natl Acad Sci U S A. 2010; 107: 10972-10977Crossref PubMed Scopus (169) Google Scholar and 3Morgan RA Dudley ME Wunderlich JR Hughes MS Yang JC Sherry RM et al.Cancer regression in patients after transfer of genetically engineered lymphocytes.Science. 2006; 314: 126-129Crossref PubMed Scopus (2122) Google Scholar), as well as the anti-NY-ESO-1 and the anti-CEA TCRs (unpublished observations). Although a great deal has been learned from the use of mouse models, the article by Bendle et al. and the analyses included in our response emphasize a potential problem of using individual mouse models to predict toxicities in the human. Had Bendle and colleagues' paper been published before the conduct of human trials utilizing TCR-transduced cells, the ability to obtain regulatory approval for these human trials would have been severely limited. This study emphasizes the need to evaluate toxicities of gene therapy in humans utilizing a careful dose-escalation approach and raises cautions about undue reliance on models in inbred mice that attempt to replicate the human clinical situation." @default.
• W2037337367 created "2016-06-24" @default.
• W2037337367 creator A5072133376 @default.
• W2037337367 date "2010-10-01" @default.
• W2037337367 modified "2023-09-23" @default.
• W2037337367 title "Of Mice, Not Men: No Evidence for Graft-versus-Host Disease in Humans Receiving T-Cell Receptor–Transduced Autologous T Cells" @default.
• W2037337367 cites W1979936799 @default.
• W2037337367 cites W2007605965 @default.
• W2037337367 cites W2050302632 @default.
• W2037337367 cites W2094652659 @default.
• W2037337367 cites W2106083290 @default.
• W2037337367 cites W2127734125 @default.
• W2037337367 doi "https://doi.org/10.1038/mt.2010.195" @default.
• W2037337367 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2951571" @default.
• W2037337367 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20885433" @default.
• W2037337367 hasPublicationYear "2010" @default.
• W2037337367 type Work @default.
• W2037337367 sameAs 2037337367 @default.
• W2037337367 citedByCount "57" @default.
• W2037337367 countsByYear W20373373672012 @default.
• W2037337367 countsByYear W20373373672013 @default.
• W2037337367 countsByYear W20373373672014 @default.
• W2037337367 countsByYear W20373373672015 @default.
• W2037337367 countsByYear W20373373672016 @default.
• W2037337367 countsByYear W20373373672017 @default.
• W2037337367 countsByYear W20373373672018 @default.
• W2037337367 countsByYear W20373373672019 @default.
• W2037337367 countsByYear W20373373672022 @default.
• W2037337367 countsByYear W20373373672023 @default.
• W2037337367 crossrefType "journal-article" @default.
• W2037337367 hasAuthorship W2037337367A5072133376 @default.
• W2037337367 hasBestOaLocation W20373373671 @default.
• W2037337367 hasConcept C126322002 @default.
• W2037337367 hasConcept C126831891 @default.
• W2037337367 hasConcept C170493617 @default.
• W2037337367 hasConcept C203014093 @default.
• W2037337367 hasConcept C2779134260 @default.
• W2037337367 hasConcept C2779972918 @default.
• W2037337367 hasConcept C54355233 @default.
• W2037337367 hasConcept C71924100 @default.
• W2037337367 hasConcept C86803240 @default.
• W2037337367 hasConceptScore W2037337367C126322002 @default.
• W2037337367 hasConceptScore W2037337367C126831891 @default.
• W2037337367 hasConceptScore W2037337367C170493617 @default.
• W2037337367 hasConceptScore W2037337367C203014093 @default.
• W2037337367 hasConceptScore W2037337367C2779134260 @default.
• W2037337367 hasConceptScore W2037337367C2779972918 @default.
• W2037337367 hasConceptScore W2037337367C54355233 @default.
• W2037337367 hasConceptScore W2037337367C71924100 @default.
• W2037337367 hasConceptScore W2037337367C86803240 @default.
• W2037337367 hasIssue "10" @default.
• W2037337367 hasLocation W20373373671 @default.
• W2037337367 hasLocation W20373373672 @default.
• W2037337367 hasLocation W20373373673 @default.
• W2037337367 hasLocation W20373373674 @default.
• W2037337367 hasOpenAccess W2037337367 @default.
• W2037337367 hasPrimaryLocation W20373373671 @default.
• W2037337367 hasRelatedWork W1614430019 @default.
• W2037337367 hasRelatedWork W198468377 @default.
• W2037337367 hasRelatedWork W2000898433 @default.
• W2037337367 hasRelatedWork W2009068171 @default.
• W2037337367 hasRelatedWork W2068012419 @default.
• W2037337367 hasRelatedWork W2319621679 @default.
• W2037337367 hasRelatedWork W3180996806 @default.
• W2037337367 hasRelatedWork W4242624046 @default.
• W2037337367 hasRelatedWork W4249153632 @default.
• W2037337367 hasRelatedWork W4249674358 @default.
• W2037337367 hasVolume "18" @default.
• W2037337367 isParatext "false" @default.
• W2037337367 isRetracted "false" @default.
• W2037337367 magId "2037337367" @default.
• W2037337367 workType "article" @default.