scholarly journals Cell Surface Antibody Retention Influences In Vivo Antitumor Activity Mediated by Antibody-dependent Cellular Cytotoxicity

2016 ◽  
Vol 36 (11) ◽  
pp. 5937-5944
Author(s):  
MASAHIRO IKEDA ◽  
KAZUNORI KATO ◽  
MIKI YAMAGUCHI ◽  
HIROFUMI HAMADA ◽  
KAZUYASU NAKAMURA ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Surface ◽  
Cellular Cytotoxicity ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
In Vivo Antitumor Activity ◽  
Surface Antibody

Co-Operativity between Antibody-Dependent Cellular Cytotoxicity (ADCC) and Immunotoxin-Mediated Killing of Human T-ALL Cells in a SCID Mouse Model: Simultaneous Delivery of Saporin Via CD7 and ADCC Via CD38 Is No Better Than the Simultaneous Delivery of Each Against Only CD7.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4517-4517
Author(s):  
David J. Flavell ◽  
Sopsamorn U. Flavell
Keyword(s):  
Cell Surface ◽  
Target Cell ◽  
Scid Mouse ◽  
Target Cells ◽  
Cellular Cytotoxicity ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Scid Mouse Model ◽  
Simultaneous Delivery ◽  
Better Than

Abstract We have previously shown that the anti-CD7 saporin-based immunotoxin (IT) HB2-SAPORIN and host antibody-dependent cellular cytotoxicity (ADCC) co-operate in the killing of human T-ALL a SCID mouse model of this disease (Flavell et al 1998 Cancer Res 58, 5787). In this described model system it is the same anti-CD7 IT that is responsible for delivering both the ribosome inactivating protein saporin and eliciting ADCC by recruiting NK cells via binding of their FcγRIIIA to the Fc domain of target cell bound IT. There is however a conflict here in that for the IT to be effective it needs to internalize whilst for maximally effective ADCC, the IT needs to remain on the cell surface in order to recruit cytotoxic effector cells. Over 90% of HB2-SAPORIN IT is internalized by CD7+ HSB-2 target cells within 12h following bivalent ligation by this IT and yet the ten percent or less of CD7 remaining on the target cell surface appears sufficient to elicit adequate ADCC to achieve the co-operative effect in vivo. The question is if ADCC is performing sub-optimally due to the reduced amount of target cell expressed CD7 doe this mean that the subsequent co-operative effect is also sub-optimal and could this be improved upon to achieve a greater and more effective target cell kill? To attempt to answer this question we have targeted saporin to the HSB-2 target cell via CD7 using a F(ab)2 IT (HB2-F(ab)2−-SAPORIN) that is incapable of eliciting ADCC whilst simultaneously delivering ADCC via an intact IgG1 anti-CD38 antibody (OKT10) that also binds to the target cell surface. The expression level of CD38 on HSB-2 cells is approximately ten-fold higher than CD7 and importantly the observed CD38 internalization rate and extent is considerably reduced compared with CD7 when ligated by cognate antibody. We therefore predicted that increased ADCC would be deliverable to HSB-2 target cells with OKT10 antibody and an in vitro chromium release assay confirmed this. However, the in vivo treatment of SCID-HSB-2 mice with a combination of HB2-F(ab)2-SAPORIN and intact OKT10 antibody was not significantly better than treatment with HB2-SAPORIN intact IT alone. These preliminary data indicate that even though additional ADCC is apparently deliverable with the OKT10 antibody this does not result in a further enhancement of the co-operative effect in vivo suggesting that the optimum co-operativity threshold has already been reached in the HB2-SAPORIN mono-therapy system.

Synthesis, in vitro and in vivo antitumor activity of symmetrical bis-Schiff base derivatives of isatin

2014 ◽  
Vol 74 ◽  
pp. 742-750 ◽  
Author(s):  
Chengyuan Liang ◽  
Juan Xia ◽  
Dong Lei ◽  
Xiang Li ◽  
Qizheng Yao ◽  
...  
Keyword(s):  
Schiff Base ◽  
Antitumor Activity ◽  
Schiff Base Derivatives ◽  
In Vivo Antitumor Activity ◽  
Derivatives Of

Unprecedented sugar-dependent in vivo antitumor activity of carbohydrate-pendant cis-diamminedichloroplatinum(II) complexes

2001 ◽  
Vol 11 (23) ◽  
pp. 3045-3047 ◽  
Author(s):  
Yuji Mikata ◽  
Yoshie Shinohara ◽  
Kazumi Yoneda ◽  
Yuka Nakamura ◽  
Izabela Brudziñska ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
In Vivo Antitumor Activity

Novel water soluble phosphate prodrugs of taxol® possessing in vivo antitumor activity

1993 ◽  
Vol 3 (8) ◽  
pp. 1761-1766 ◽  
Author(s):  
Yasutsugu Ueda ◽  
Amarendra B. Mikkilineni ◽  
Jay O. Knipe ◽  
William C. Rose ◽  
Anna Maria Casazza ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Water Soluble ◽  
Soluble Phosphate ◽  
In Vivo Antitumor Activity
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