Linked Life Data

12393660

Source:http://linkedlifedata.com/resource/pubmed/id/12393660

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-1-1
pubmed:abstractText
Cytokine gene-modified tumor cells have increased immunogenicity and retain the antigenic repertoire of a particular neoplasia. However, practical concerns have led to an increased interest in allogeneic gene-transduced bystander cells as a broader source of cytokines for autologous tumor cell-based vaccines. Here, we show that allogeneic B78H1 major histocompatibility complex (MHC) class I-negative and -positive (H-2K(b)- and D(b)-transfected) cells induced cytotoxic T lymphocytes (CTLs) and protection in BALB/c mice at comparable levels in response to a challenge with C26 (H-2(d)) colon carcinoma cells sharing the tumor-associated antigen envelope glycoprotein 70 (env-gp70) with both cell lines. Class I-negative B78H1 cells transduced to express interleukin-12 (IL-12) and mixed with autologous A20 tumor cells led to eradication of preestablished A20 lymphoma in 50% or 100% of treated mice after 3 or 4 vaccinations, respectively, whereas A20 cells alone or mixed with nontransduced B78H1 cured none or 50% of mice after 3 or 4 vaccinations, respectively. Immunization with the IL-12-producing bystander cell line increased tumor-specific proliferation and type 1 cytokine production by CD4(+) T cells. By contrast, CD4 T-cell function appeared impaired after immunization with A20 cells alone or mixed with B78H1 cells. Indeed, only CD4(+) T cells from IL-12-treated mice could be restimulated with anti-OX40 monoclonal antibody (mAb) in place of a fourth cellular boost. Moreover, the IL-12-based tumor vaccine induced expansion of tumor-specific interferon-gamma (IFN-gamma)-producing CD8(+) T cells. These results are clinically relevant for the development of feasible IL-12 cancer vaccines based on engineered class I-negative bystander cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
568-75
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12393660-Animals, pubmed-meshheading:12393660-Antigens, CD27, pubmed-meshheading:12393660-Bystander Effect, pubmed-meshheading:12393660-Cancer Vaccines, pubmed-meshheading:12393660-Cytokines, pubmed-meshheading:12393660-Histocompatibility Antigens Class I, pubmed-meshheading:12393660-Immunity, Cellular, pubmed-meshheading:12393660-Interleukin-12, pubmed-meshheading:12393660-Lymphocyte Activation, pubmed-meshheading:12393660-Lymphoma, pubmed-meshheading:12393660-Mice, pubmed-meshheading:12393660-Mice, Inbred BALB C, pubmed-meshheading:12393660-Neoplasms, Experimental, pubmed-meshheading:12393660-Receptors, OX40, pubmed-meshheading:12393660-Receptors, Tumor Necrosis Factor, pubmed-meshheading:12393660-T-Lymphocytes, Cytotoxic, pubmed-meshheading:12393660-Transduction, Genetic, pubmed-meshheading:12393660-Treatment Outcome, pubmed-meshheading:12393660-Tumor Cells, Cultured
pubmed:year
2003
pubmed:articleTitle
Autologous and MHC class I-negative allogeneic tumor cells secreting IL-12 together cure disseminated A20 lymphoma.
pubmed:affiliation
Immunotherapy and Gene Therapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't