PMID- 9396606
OWN - NLM
STAT- MEDLINE
DCOM- 19980109
LR  - 20190914
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 3
IP  - 12
DP  - 1997 Dec
TI  - Tumor regression with regional distribution of the targeted toxin TF-CRM107 in 
      patients with malignant brain tumors.
PG  - 1362-8
AB  - We investigated regional therapy of recurrent malignant brain tumors with 
      transferrin-CRM107, a conjugate of human transferrin (Tf) and a genetic mutant of 
      diphtheria toxin (CRM107) that lacks native toxin binding. Physiological barriers 
      to delivering proteins to tumor and surrounding infiltrated brain were 
      circumvented with high-flow interstitial microinfusion. At least a 50% reduction 
      in tumor volume on magnetic resonance imaging (MRI) occurred in 9 of 15 patients 
      who could be evaluated (60%), including two complete responses. Peritumoral 
      toxicity developed 1-4 weeks after treatment in three of three patients at 1.0 
      microg/ml, but in zero of nine patients treated at lower concentrations. No 
      symptomatic systemic toxicity occurred. Regional perfusion with Tf-CRM107 
      produces tumor responses without systemic toxicity in patients with malignant 
      brain tumors refractory to conventional therapy. Direct interstitial infusion can 
      be used successfully to distribute a large protein in the tumor and infiltrated 
      brain surrounding the tumor.
FAU - Laske, D W
AU  - Laske DW
AD  - Surgical Neurology Branch, National Institute of Neurological Disorders and 
      Stroke, National Institutes of Health, Bethesda, Maryland 20892-1414, USA.
FAU - Youle, R J
AU  - Youle RJ
FAU - Oldfield, E H
AU  - Oldfield EH
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Antibodies)
RN  - 0 (Diphtheria Toxin)
RN  - 0 (Transferrin)
SB  - IM
CIN - Nat Med. 1997 Dec;3(12):1323. PMID: 9396599
MH  - Adult
MH  - Aged
MH  - Antibodies/blood
MH  - Brain/metabolism/pathology
MH  - Brain Neoplasms/pathology/*therapy
MH  - Diphtheria Toxin/adverse effects/genetics/*therapeutic use
MH  - Drug Design
MH  - Female
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Transferrin/adverse effects/genetics/*therapeutic use
EDAT- 1997/12/13 00:00
MHDA- 1997/12/13 00:01
CRDT- 1997/12/13 00:00
PHST- 1997/12/13 00:00 [pubmed]
PHST- 1997/12/13 00:01 [medline]
PHST- 1997/12/13 00:00 [entrez]
AID - 10.1038/nm1297-1362 [doi]
PST - ppublish
SO  - Nat Med. 1997 Dec;3(12):1362-8. doi: 10.1038/nm1297-1362.