Efficacy of transferrin receptor-targeted immunotoxins in brain tumor cell lines and pediatric brain tumors

Lori A. Martell, Alka Agrawal, Donald (Don) Ross, Karin M. Muraszko

Research output: Contribution to journalArticle

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Abstract

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 109-1010 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 × 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.

Original languageEnglish (US)
Pages (from-to)1348-1353
Number of pages6
JournalCancer Research
Volume53
Issue number6
StatePublished - Mar 15 1993
Externally publishedYes

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Immunotoxins
Transferrin Receptors
Tumor Cell Line
Brain Neoplasms
Pediatrics
Medulloblastoma
Neoplasms
Glioblastoma
Cell Line
Proteins
Neuroblastoma
Inhibitory Concentration 50
Cell Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Efficacy of transferrin receptor-targeted immunotoxins in brain tumor cell lines and pediatric brain tumors. / Martell, Lori A.; Agrawal, Alka; Ross, Donald (Don); Muraszko, Karin M.

In: Cancer Research, Vol. 53, No. 6, 15.03.1993, p. 1348-1353.

Research output: Contribution to journalArticle

Martell, Lori A. ; Agrawal, Alka ; Ross, Donald (Don) ; Muraszko, Karin M. / Efficacy of transferrin receptor-targeted immunotoxins in brain tumor cell lines and pediatric brain tumors. In: Cancer Research. 1993 ; Vol. 53, No. 6. pp. 1348-1353.
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