PMID- 8443815
OWN - NLM
STAT- MEDLINE
DCOM- 19930407
LR  - 20210108
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 53
IP  - 6
DP  - 1993 Mar 15
TI  - Efficacy of transferrin receptor-targeted immunotoxins in brain tumor cell lines 
      and pediatric brain tumors.
PG  - 1348-53
AB  - The efficacy and cytotoxic properties of immunotoxin conjugates directed against 
      the transferrin receptor were examined in cell lines and operative specimens from 
      pediatric brain tumors. Dose-response relationships were assessed for 
      immunotoxin-mediated inhibition of protein synthesis for two immunotoxins, 
      454A12-rRA and anti-tfnR-CRM 107. Three target medulloblastoma cell lines (DAOY, 
      D283MED, and D341MED), a glioblastoma (U373), and a neuroblastoma (SH-SY5Y) cell 
      line exhibited similar sensitivity to both immunotoxins with IC50s in the 
      10(-9)-10(-10) M range. The time course of protein synthesis inhibition by the 
      immunotoxins in DAOY cells showed that inhibition by anti-tfnR-CRM 107 was rapid 
      and apparent by 6 h of incubation. In contrast, a response to 454A12-rRA was not 
      observed until 16 h. Cell viability was decreased 30-40% by 24 h after removing 
      454A12-rRA (1 x 10(-9) M) and was maximally decreased 70-80% after 3 days. The 
      efficacy of the immunotoxins on a variety of fresh specimens of pediatric brain 
      tumors was also examined. The more aggressive and malignant tumor types such as 
      glioblastoma multiforme and medulloblastoma had low IC50 values (10(-12) M), 
      indicating that these tumors were extremely sensitive to transferrin 
      receptor-targeted immunotoxins. In general, protein synthesis in slow-growing and 
      benign tumors was not as greatly affected by immunotoxins. Immunoblots showed 
      expression of transferrin receptors on the cell lines and tumors which correlated 
      with in vitro sensitivity to immunotoxin. The results demonstrate that two 
      immunotoxins targeted to the transferrin receptor are efficacious in killing 
      brain tumor cell lines and primary tumor cultures at very low concentrations and 
      that highly malignant tumors are especially sensitive to this cytotoxic response.
FAU - Martell, L A
AU  - Martell LA
AD  - Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109.
FAU - Agrawal, A
AU  - Agrawal A
FAU - Ross, D A
AU  - Ross DA
FAU - Muraszko, K M
AU  - Muraszko KM
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 (Immunotoxins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Receptors, Transferrin)
RN  - 9009-86-3 (Ricin)
SB  - IM
MH  - Brain Neoplasms/*pathology/therapy
MH  - Cell Survival/drug effects
MH  - Child
MH  - Glioma/pathology/therapy
MH  - Humans
MH  - Immunotoxins/*pharmacology/therapeutic use
MH  - Medulloblastoma/pathology/therapy
MH  - Neoplasm Proteins/biosynthesis
MH  - Neuroblastoma/pathology/therapy
MH  - Receptors, Transferrin/analysis/*immunology
MH  - Ricin/*pharmacology/therapeutic use
MH  - Tumor Cells, Cultured
EDAT- 1993/03/15 00:00
MHDA- 1993/03/15 00:01
CRDT- 1993/03/15 00:00
PHST- 1993/03/15 00:00 [pubmed]
PHST- 1993/03/15 00:01 [medline]
PHST- 1993/03/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1993 Mar 15;53(6):1348-53.