Source:http://linkedlifedata.com/resource/pubmed/id/12384531
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
20
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| pubmed:dateCreated |
2002-10-17
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| pubmed:abstractText |
The therapeutic efficacy of combined antiangiogenic and immune therapy was tested against weakly immunogenic and highly metastatic 4T1 breast tumor using SU6668, an angiogenesis inhibitor and recombinant murine (rm) B7.2-IgG fusion protein, an immunostimulator. SU6668 inhibits the tyrosine kinase activity of three angiogenic receptors VEGFR2 (Flk-1/KDR), PDGFRbeta, and FGFR1, which play a crucial role in tumor-induced vascularization. rmB7.2-IgG is a fusion protein of the extracellular domain of B7.2, and the hinge and constant domains of murine IgG2a. Intermolecule disulfide linkages are maintained so that it forms a dimer. Our studies showed that three weekly immunizations of BALB/c mice bearing 0.5-0.8 cm 4T1 breast tumors with rmB7.2-IgG and irradiated 4T1 tumor cells (B7.2-IgG/TC) resulted in a significant inhibition of tumor growth and formation of pulmonary metastases. T-cell depletion experiments revealed that both CD4(+) and CD8(+) T lymphocytes are required for stimulation of the antitumor and antimetastatic immune response by B7.2-IgG/TC. Treatment of mice with SU6668 substantially inhibited tumor vascularization but did not inhibit tumor infiltration by T lymphocytes or the T-cell response to rmB7.2-IgG therapy. On the contrary, tumors in mice immunized with B7.2-IgG/TC and treated with SU6668 had higher numbers of tumor infiltrating T cells than tumors of other groups. SU6668 treatments initiated either on day 3 or day 10 after inoculation of 4T1 tumor cells resulted in a significant inhibition of tumor growth. Similarly, three weekly immunizations with B7.2-IgG/TC starting either on day 7 or 12 inhibited growth of 4T1 tumors. However, the most potent antitumor effects were observed in mice treated with a combination of SU6668 and B7.2-IgG/TC. Analysis of pulmonary metastases revealed that combined therapy also had a more potent antimetastatic effect than each modality alone. These results indicate that antiangiogenic and immune therapies using SU6668 and B7.2-IgG/TC are compatible, and manifest complementary antitumor and antimetastatic effects. Combined antiangiogenic and immune therapy might represent a new strategy for cancer treatment.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiogenesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD86,
http://linkedlifedata.com/resource/pubmed/chemical/Cancer Vaccines,
http://linkedlifedata.com/resource/pubmed/chemical/Cd86 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrroles,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SU 6668
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0008-5472
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
62
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
5727-35
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:12384531-Angiogenesis Inhibitors,
pubmed-meshheading:12384531-Animals,
pubmed-meshheading:12384531-Antigens, CD,
pubmed-meshheading:12384531-Antigens, CD86,
pubmed-meshheading:12384531-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:12384531-CD4-Positive T-Lymphocytes,
pubmed-meshheading:12384531-CD8-Positive T-Lymphocytes,
pubmed-meshheading:12384531-Cancer Vaccines,
pubmed-meshheading:12384531-Combined Modality Therapy,
pubmed-meshheading:12384531-Female,
pubmed-meshheading:12384531-Immunoglobulin G,
pubmed-meshheading:12384531-Indoles,
pubmed-meshheading:12384531-Interferon-gamma,
pubmed-meshheading:12384531-Lymphocyte Activation,
pubmed-meshheading:12384531-Lymphocytes, Tumor-Infiltrating,
pubmed-meshheading:12384531-Mammary Neoplasms, Experimental,
pubmed-meshheading:12384531-Membrane Glycoproteins,
pubmed-meshheading:12384531-Mice,
pubmed-meshheading:12384531-Mice, Inbred BALB C,
pubmed-meshheading:12384531-Neoplasm Metastasis,
pubmed-meshheading:12384531-Protein-Tyrosine Kinases,
pubmed-meshheading:12384531-Pyrroles,
pubmed-meshheading:12384531-Recombinant Fusion Proteins,
pubmed-meshheading:12384531-Spleen
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| pubmed:year |
2002
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| pubmed:articleTitle |
Combined therapy of local and metastatic 4T1 breast tumor in mice using SU6668, an inhibitor of angiogenic receptor tyrosine kinases, and the immunostimulator B7.2-IgG fusion protein.
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| pubmed:affiliation |
Department of Pathology and University of Pittsburgh Cancer Institute, Pennsylvania 15213, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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