Linked Life Data

16230420

Source:http://linkedlifedata.com/resource/pubmed/id/16230420

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2005-10-18
pubmed:abstractText
T-cell adoptive immunotherapy for stringent murine tumor models, such as intracranial, s.c., or advanced pulmonary metastases, routinely uses lymphodepletive conditioning regimens before T-cell transfer, like recent clinical protocols. In this study, we examined whether host lymphodepletion is an obligatory component of curative T-cell therapy; we also examined the mechanism by which it augments therapy. Mice bearing intracranial, s.c., or 10-day pulmonary metastases of MCA 205 received total body irradiation conditioning or were nonirradiated before i.v. transfer of tumor-reactive T cells. Total body irradiation was not required for immunologically specific curative therapy and induction of memory provided that a 3- to 12-fold higher T-cell dose was administered. The mechanism involved enhanced intratumoral proliferation of T-effector cells in total body irradiation-conditioned recipients. In this tumor model, intratumoral T(reg) cells were not detected; consequently, intratumoral T-effector cells produced identical amounts of IFN-gamma upon ex vivo antigen stimulation irrespective of total body irradiation conditioning. Thus, host lymphodepletion augments T-cell immunotherapy through enhanced antigen-driven proliferation of T-effector cells, but curative therapy can be achieved in nonconditioned hosts by escalation of T-cell dose. These data provide a rationale for dose escalation of T-effector cells in situations where single or repeated lymphodepletion regimens are contraindicated.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9547-54
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Host lymphodepletion augments T cell adoptive immunotherapy through enhanced intratumoral proliferation of effector cells.
pubmed:affiliation
Center for Surgery Research, Division of Surgery, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural