Document Detail

In vivo antitumor activity of anti-CD3-induced activated killer cells.
MedLine Citation:
PMID:  2527087     Owner:  NLM     Status:  MEDLINE    
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)
Y S Yun; M E Hargrove; C C Ting
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer research     Volume:  49     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1989 Sep 
Date Detail:
Created Date:  1989-09-15     Completed Date:  1989-09-15     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4770-4     Citation Subset:  IM    
Division of Cancer Biology and Diagnosis, National Cancer Institute, Bethesda, Maryland 20892.
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MeSH Terms
Antibodies, Monoclonal / immunology*
Antigens, CD3
Antigens, Differentiation, T-Lymphocyte / immunology*
Cytotoxicity, Immunologic
Immunotherapy / methods
Interleukin-2 / pharmacology
Killer Cells, Natural / immunology*,  transplantation
Lymphocyte Activation
Mice, Inbred DBA
Neoplasm Transplantation
Neoplasms, Experimental / therapy*
Receptors, Antigen, T-Cell / immunology*
T-Lymphocytes / classification
Tumor Cells, Cultured
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD3; 0/Antigens, Differentiation, T-Lymphocyte; 0/Interleukin-2; 0/Receptors, Antigen, T-Cell

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