PMID- 1643636
OWN - NLM
STAT- MEDLINE
DCOM- 19920910
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 52
IP  - 16
DP  - 1992 Aug 15
TI  - Cytotoxicity of streptavidin-blocked biotinyl-ricin is retrieved by in vitro 
      immunotargeting via biotinyl monoclonal antibody.
PG  - 4448-52
AB  - The streptavidin-biotin system has been used to immunotarget whole ricin to tumor 
      cells in a system that overcomes ricin-nonspecific cytotoxicity. Biotin was 
      linked to ricin via a disulfide-containing reagent, 
      sulfosuccinimidyl-2-(biotinamido)ethyl-1,3'-dithiopropionate. The product, 
      biotinyl-S,S-ricin (b-ricin), retained most of its in vitro cytotoxic activity 
      against human epidermoid carcinoma (KB) cells. Complexing b-ricin to streptavidin 
      resulted in greater than 99% loss of its cellular toxicity which is associated 
      with loss of cell-binding activity. The streptavidin-b-ricin complex could, 
      however, be targeted to KB cells via the biotinylated monoclonal antibody 108 
      which is specific to the epidermal growth factor receptor overexpressed on KB 
      cells. The complex did not regain its activity if the specific antibody was not 
      biotinylated or if the biotinylated antibody was of a different specificity. 
      Streptavidin is thus used to block b-ricin, presumably due to a steric restraint 
      of the streptavidin on the ricin B-chain, and to bridge it to biotinyl antibody 
      recognizing the target cell. Avidin could not replace streptavidin in this system 
      since a complex between b-ricin and avidin retained a major part (60%) of ricin 
      cytotoxic activity. This is attributed to the nonspecific binding of avidin to 
      cells in vitro, including the KB cells. It is suggested that b-ricin is blocked 
      by both streptavidin and avidin, but once the complex gains access to the cell 
      surface, its cytotoxic activity is specifically retrieved.
FAU - Schechter, B
AU  - Schechter B
AD  - Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, 
      Israel.
FAU - Arnon, R
AU  - Arnon R
FAU - Wilchek, M
AU  - Wilchek M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Bacterial Proteins)
RN  - 0 (Immunotoxins)
RN  - 1405-69-2 (Avidin)
RN  - 6SO6U10H04 (Biotin)
RN  - 9009-86-3 (Ricin)
RN  - 9013-20-1 (Streptavidin)
SB  - IM
MH  - Avidin/pharmacology
MH  - Bacterial Proteins/*pharmacology
MH  - Biotin/pharmacology
MH  - Carcinoma, Squamous Cell/*drug therapy
MH  - Drug Screening Assays, Antitumor
MH  - Humans
MH  - Immunotoxins/chemistry/*therapeutic use
MH  - Mouth Neoplasms/*drug therapy
MH  - Ricin/*chemistry
MH  - Streptavidin
MH  - Tumor Cells, Cultured
EDAT- 1992/08/15 00:00
MHDA- 1992/08/15 00:01
CRDT- 1992/08/15 00:00
PHST- 1992/08/15 00:00 [pubmed]
PHST- 1992/08/15 00:01 [medline]
PHST- 1992/08/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1992 Aug 15;52(16):4448-52.