PMID- 12034862
OWN - NLM
STAT- MEDLINE
DCOM- 20030711
LR  - 20190910
IS  - 0269-2139 (Print)
IS  - 0269-2139 (Linking)
VI  - 15
IP  - 5
DP  - 2002 May
TI  - Targeting glioblastoma multiforme with an IL-13/diphtheria toxin fusion protein 
      in vitro and in vivo in nude mice.
PG  - 419-27
AB  - Fusion proteins composed of tumor binding agents and potent catalytic toxins show 
      promise for intracranial therapy of brain cancer and an advantage over systemic 
      therapy. Glioblastoma multiforme (GBM) is the most common form of brain cancer 
      and overexpresses IL-13R. Thus, we developed an interleukin-13 receptor targeting 
      fusion protein, DT(390)IL13, composed of human interleukin-13 and the first 389 
      amino acids of diphtheria toxin. To measure its ability to inhibit GBM, 
      DT(390)IL13 was tested in vitro and found to inhibit selectively the U373 MG GBM 
      cell line with an IC(50) around 12 pmol/l. Cytotoxicity was neutralized by 
      anti-human-interleukin-13 antibody, but not by control antibodies. In vivo, small 
      U373 MG glioblastoma xenografts in nude mice completely regressed in most animals 
      after five intratumoral injections of 1 microg of DT(390)IL13 q.o.d., but not by 
      the control fusion protein DT(390)IL-2. DT(390)IL13 was also tested against 
      primary explant GBM cells of a patient's excised tumor and the IC(50) was similar 
      to that measured for U373 MG. Further studies showed a therapeutic window for 
      DT(390)IL13 of 1-30 microg/injection and histology studies and enzyme 
      measurements showed that the maximum tolerated dose of DT(390)IL13 had little 
      effect on kidney, liver, spleen, lung and heart in non-tumor-bearing 
      immunocompetent mice. Together, these data suggest that DT(390)IL13 may provide 
      an important, alternative therapy for brain cancer.
FAU - Li, Chunbin
AU  - Li C
AD  - Department of Therapeutic Radiology-Radiation Oncology, Section on Experimental 
      Cancer Immunology, University of Minnesota Cancer Center, University of 
      Minnesota, Minneapolis, MN 55455, USA.
FAU - Hall, Walter A
AU  - Hall WA
FAU - Jin, Ni
AU  - Jin N
FAU - Todhunter, Deborah A
AU  - Todhunter DA
FAU - Panoskaltsis-Mortari, Angela
AU  - Panoskaltsis-Mortari A
FAU - Vallera, Daniel A
AU  - Vallera DA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Protein Eng
JT  - Protein engineering
JID - 8801484
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Diphtheria Toxin)
RN  - 0 (IL13RA1 protein, human)
RN  - 0 (Il13ra1 protein, mouse)
RN  - 0 (Interleukin-13)
RN  - 0 (Interleukin-13 Receptor alpha1 Subunit)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-13)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*administration & dosage/therapeutic use
MH  - Diphtheria Toxin/*administration & dosage/therapeutic use
MH  - Drug Delivery Systems
MH  - Drug Screening Assays, Antitumor
MH  - Female
MH  - Glioblastoma/*drug therapy
MH  - In Vitro Techniques
MH  - Interleukin-13/*administration & dosage/therapeutic use
MH  - Interleukin-13 Receptor alpha1 Subunit
MH  - Kinetics
MH  - Maximum Tolerated Dose
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Nude
MH  - Neoplasm Transplantation
MH  - Receptors, Interleukin/metabolism
MH  - Receptors, Interleukin-13
MH  - Recombinant Fusion Proteins/administration & dosage
EDAT- 2002/05/30 10:00
MHDA- 2003/07/12 05:00
CRDT- 2002/05/30 10:00
PHST- 2002/05/30 10:00 [pubmed]
PHST- 2003/07/12 05:00 [medline]
PHST- 2002/05/30 10:00 [entrez]
AID - 10.1093/protein/15.5.419 [doi]
PST - ppublish
SO  - Protein Eng. 2002 May;15(5):419-27. doi: 10.1093/protein/15.5.419.