| In vivo antitumor activity of anti-CD3-induced activated killer cells. | |
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MedLine Citation:
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PMID: 2527087 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study investigates the potential of the alpha CD3-induced killer cells for use in adoptive immunotherapy of tumor growth. The alpha CD3-induced, activated, killer cells (CD3-AK) were generated in DBA/2 (H-2d) splenocytes by preactivation with alpha CD3 and were then cultured in the presence (CD3-AK [alpha CD3+]) or absence (CD3-AK [alpha CD3-]) of alpha CD3. The conventional lymphokine-activated killer (LAK) cells were induced by culturing DBA/2 splenocytes with purified human recombinant interleukin 2. Testing their in vitro cytotoxicity against syngeneic mastocytoma P815, CD3-AK (alpha CD3+) cells gave the highest levels of cytotoxicity and were 20-fold higher than LAK cells and 200-fold higher than CD3-AK (alpha CD3-) cells. However, the cytotoxic activity of LAK or CD3-AK (alpha CD3-) cells was augmented by preincubating them with alpha CD3 for 3 h; then, the difference in cytotoxic activity was reduced from 20- to 4-fold and from 200- to 2-fold, respectively. The in vivo antitumor activity of these killer cells paralleled the in vitro activity. In tests using tumor neutralization experiments, 80-100% of the mice that were challenged with 1 x 10(2) P815 cells remained tumor free after receiving 5 x 10(6) CD3-AK (alpha CD3+) cells. When the challenge dose increased to 1 x 10(3) and to 1 x 10(4) cells, giving CD3-AK (alpha CD3+) cells slowed down the rate of tumor growth but only 20% of the mice remained tumor free. The untreated LAK cells or CD3-AK (alpha CD3-) cells did not induce any protection. After preincubation with alpha CD3 for 3 h, the CD3-AK (alpha CD3-) cells provided protection in 30% of the challenged mice. The phenotype of effectors for mediating the in vitro and in vivo antitumor activities was found to be Thy1+, CD4-, and CD8+ cells. Flow microfluorometry analysis showed that the higher levels of cytotoxic activity obtained with CD3-AK (alpha CD3+) cells could not be simply explained by the increase of CD8+ cells, and the cytotoxic activity of individual CD3-AK (alpha CD3+) cells appeared to be much higher than that of the LAK cells. After tumor growth was established for 1-2 days, giving CD3-AK (alpha CD3+) cells slowed down the rate of tumor growth, and 20% of the mice remained tumor free. These results indicate that CD3-AK cells may be used in the immunotherapy of tumor growth.(ABSTRACT TRUNCATED AT 400 WORDS) |
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Authors:
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Y S Yun; M E Hargrove; C C Ting |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Cancer research Volume: 49 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 1989 Sep |
Date Detail:
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Created Date: 1989-09-15 Completed Date: 1989-09-15 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 4770-4 Citation Subset: IM |
Affiliation:
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Division of Cancer Biology and Diagnosis, National Cancer Institute, Bethesda, Maryland 20892. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / immunology* Antigens, CD3 Antigens, Differentiation, T-Lymphocyte / immunology* Cytotoxicity, Immunologic Female Immunotherapy / methods Interleukin-2 / pharmacology Killer Cells, Natural / immunology*, transplantation Lymphocyte Activation Mice Mice, Inbred DBA Neoplasm Transplantation Neoplasms, Experimental / therapy* Phenotype Receptors, Antigen, T-Cell / immunology* T-Lymphocytes / classification Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Antigens, CD3; 0/Antigens, Differentiation, T-Lymphocyte; 0/Interleukin-2; 0/Receptors, Antigen, T-Cell |
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