Linked Life Data

17145892

Source:http://linkedlifedata.com/resource/pubmed/id/17145892

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2006-12-5
pubmed:abstractText
Allogeneic cell therapy as a means to break immunotolerance to solid tumors is increasingly used for cancer treatment. To investigate cellular alloimmune responses in a human tumor model, primary cultures were established from renal cell carcinoma (RCC) tissues of 56 patients. In three patients with stable RCC line and human leukocyte antigen (HLA)-identical sibling donor available, allogeneic and autologous RCC reactivities were compared using mixed lymphocyte/tumor cell cultures (MLTC). Responding lymphocytes were exclusively CD8(+) T cells, whereas CD4(+) T cells or natural killer cells were never observed. Sibling MLTC populations showed higher proliferative and cytolytic antitumor responses compared with their autologous counterparts. The allo-MLTC responders originated from the CD8(+) CD62L(high)(+) peripheral blood subpopulation containing naive precursor and central memory T cells. Limiting dilution cloning failed to establish CTL clones from autologous MLTCs or tumor-infiltrating lymphocytes. In contrast, a broad panel of RCC-reactive CTL clones was expanded from each allogeneic MLTC. These sibling CTL clones either recognized exclusively the original RCC tumor line or cross-reacted with nonmalignant kidney cells of patient origin. A minority of CTL clones also recognized patient-derived hematopoietic cells or other allogeneic tumor targets. The MHC-restricting alleles for RCC-reactive sibling CTL clones included HLA-A2, HLA-A3, HLA-A11, HLA-A24, and HLA-B7. In one sibling donor-RCC pair, strongly proliferative CD3(+)CD16(+)CD57(+) CTL clones with non-HLA-restricted antitumor reactivity were established. Our results show superior tumor-reactive CD8 responses of matched allogeneic compared with autologous T cells. These data encourage the generation of antitumor T-cell products from HLA-identical siblings and their potential use in adoptive immunotherapy of metastatic RCC patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11447-54
pubmed:meshHeading
pubmed-meshheading:17145892-Antibodies, Monoclonal, pubmed-meshheading:17145892-Antibody Specificity, pubmed-meshheading:17145892-Antigens, CD3, pubmed-meshheading:17145892-Antigens, CD8, pubmed-meshheading:17145892-CD8-Positive T-Lymphocytes, pubmed-meshheading:17145892-Carcinoma, Renal Cell, pubmed-meshheading:17145892-Cell Line, Tumor, pubmed-meshheading:17145892-Cell Proliferation, pubmed-meshheading:17145892-Cell Survival, pubmed-meshheading:17145892-Cytotoxicity, Immunologic, pubmed-meshheading:17145892-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:17145892-Flow Cytometry, pubmed-meshheading:17145892-HLA Antigens, pubmed-meshheading:17145892-Humans, pubmed-meshheading:17145892-Kidney Neoplasms, pubmed-meshheading:17145892-L-Selectin, pubmed-meshheading:17145892-Lymphocytes, Tumor-Infiltrating, pubmed-meshheading:17145892-Siblings, pubmed-meshheading:17145892-T-Lymphocytes, Cytotoxic, pubmed-meshheading:17145892-Tumor Cells, Cultured
pubmed:year
2006
pubmed:articleTitle
Superior antitumor in vitro responses of allogeneic matched sibling compared with autologous patient CD8+ T cells.
pubmed:affiliation
Department of Medicine III, Hematology and Oncology, University of Mainz, Mainz, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't