Dexamethasone decreases the delivery of tumor-specific monoclonal antibody to both intracerebral and subcutaneous tumor xenografts

Edward Neuwelt, Peggy A. Barnett, Fred L. Ramsey, Ingegerd Hellstr;Ouml;M, Karl Erik Hellstr;Ouml;M, Christopher I. McCormick

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

THE EFFECT OF dexamethasone on the delivery of monoclonal antibody L6 IgG to intracerebral and subcutaneous LX-1 small cell lung carcinoma xenografts was evaluated in nude rats (n = 157). Dexamethasone (0, 8, or 24 mg/m2) was given 18 hours before infusion of L6 IgG, with or without osmotic disruption of the blood-brain barrier. Compared with controls, the 8 mg/m2 dose decreased delivery of L6 IgG (12–37%) to all tissues, but the only significant decrease (P <0.001) was in the subcutaneous tumor (37%). In the 24 mg/m2 group, L6 IgG delivery was significantly (P <0.001) decreased to all tissues (37–60%). Dexamethasone had no effect on plasma levels. Barrier disruption significantly (P <0.0001) increased L6 IgG delivery to intracranial tumor and surrounding brain, but not to subcutaneous tumor or plasma. The percentage of decremental effect of dexamethasone on L6 IgG delivery was the same with and without barrier disruption and was not associated with the time the animals were killed (P > 0.05). Compared with controls, the ratio of intracranial tumor to normal brain showed no change with dexamethasone, but the ratios of both intracranial and subcutaneous tumors to plasma significantly (P <0.002) decreased with both doses. The in vitro cell binding capacity of L6 IgG to LX-1 cells remained unchanged after incubation of cells with dexamethasone over a 3-log concentration for 4 days, demonstrating no effect on antigen expression. This study suggests that dexamethasone has a clinically relevant generalized (i.e., central nervous system and systemic) vascular effect on permeability to L6 IgG monoclonal antibody.

Original languageEnglish (US)
Pages (from-to)478-484
Number of pages7
JournalNeurosurgery
Volume33
Issue number3
StatePublished - 1993

Fingerprint

Heterografts
Dexamethasone
Immunoglobulin G
Monoclonal Antibodies
Neoplasms
Nude Rats
Small Cell Lung Carcinoma
Blood-Brain Barrier
Blood Vessels
Permeability
Central Nervous System
Antigens
Brain

Keywords

  • Blood-brain barrier
  • Brain tumors
  • Immunotherapy
  • Permeability
  • Steroids

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Neuwelt, E., Barnett, P. A., Ramsey, F. L., Hellstr;Ouml;M, I., Hellstr;Ouml;M, K. E., & McCormick, C. I. (1993). Dexamethasone decreases the delivery of tumor-specific monoclonal antibody to both intracerebral and subcutaneous tumor xenografts. Neurosurgery, 33(3), 478-484.

Dexamethasone decreases the delivery of tumor-specific monoclonal antibody to both intracerebral and subcutaneous tumor xenografts. / Neuwelt, Edward; Barnett, Peggy A.; Ramsey, Fred L.; Hellstr;Ouml;M, Ingegerd; Hellstr;Ouml;M, Karl Erik; McCormick, Christopher I.

In: Neurosurgery, Vol. 33, No. 3, 1993, p. 478-484.

Research output: Contribution to journalArticle

Neuwelt, E, Barnett, PA, Ramsey, FL, Hellstr;Ouml;M, I, Hellstr;Ouml;M, KE & McCormick, CI 1993, 'Dexamethasone decreases the delivery of tumor-specific monoclonal antibody to both intracerebral and subcutaneous tumor xenografts', Neurosurgery, vol. 33, no. 3, pp. 478-484.
Neuwelt, Edward ; Barnett, Peggy A. ; Ramsey, Fred L. ; Hellstr;Ouml;M, Ingegerd ; Hellstr;Ouml;M, Karl Erik ; McCormick, Christopher I. / Dexamethasone decreases the delivery of tumor-specific monoclonal antibody to both intracerebral and subcutaneous tumor xenografts. In: Neurosurgery. 1993 ; Vol. 33, No. 3. pp. 478-484.
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N2 - THE EFFECT OF dexamethasone on the delivery of monoclonal antibody L6 IgG to intracerebral and subcutaneous LX-1 small cell lung carcinoma xenografts was evaluated in nude rats (n = 157). Dexamethasone (0, 8, or 24 mg/m2) was given 18 hours before infusion of L6 IgG, with or without osmotic disruption of the blood-brain barrier. Compared with controls, the 8 mg/m2 dose decreased delivery of L6 IgG (12–37%) to all tissues, but the only significant decrease (P <0.001) was in the subcutaneous tumor (37%). In the 24 mg/m2 group, L6 IgG delivery was significantly (P <0.001) decreased to all tissues (37–60%). Dexamethasone had no effect on plasma levels. Barrier disruption significantly (P <0.0001) increased L6 IgG delivery to intracranial tumor and surrounding brain, but not to subcutaneous tumor or plasma. The percentage of decremental effect of dexamethasone on L6 IgG delivery was the same with and without barrier disruption and was not associated with the time the animals were killed (P > 0.05). Compared with controls, the ratio of intracranial tumor to normal brain showed no change with dexamethasone, but the ratios of both intracranial and subcutaneous tumors to plasma significantly (P <0.002) decreased with both doses. The in vitro cell binding capacity of L6 IgG to LX-1 cells remained unchanged after incubation of cells with dexamethasone over a 3-log concentration for 4 days, demonstrating no effect on antigen expression. This study suggests that dexamethasone has a clinically relevant generalized (i.e., central nervous system and systemic) vascular effect on permeability to L6 IgG monoclonal antibody.

AB - THE EFFECT OF dexamethasone on the delivery of monoclonal antibody L6 IgG to intracerebral and subcutaneous LX-1 small cell lung carcinoma xenografts was evaluated in nude rats (n = 157). Dexamethasone (0, 8, or 24 mg/m2) was given 18 hours before infusion of L6 IgG, with or without osmotic disruption of the blood-brain barrier. Compared with controls, the 8 mg/m2 dose decreased delivery of L6 IgG (12–37%) to all tissues, but the only significant decrease (P <0.001) was in the subcutaneous tumor (37%). In the 24 mg/m2 group, L6 IgG delivery was significantly (P <0.001) decreased to all tissues (37–60%). Dexamethasone had no effect on plasma levels. Barrier disruption significantly (P <0.0001) increased L6 IgG delivery to intracranial tumor and surrounding brain, but not to subcutaneous tumor or plasma. The percentage of decremental effect of dexamethasone on L6 IgG delivery was the same with and without barrier disruption and was not associated with the time the animals were killed (P > 0.05). Compared with controls, the ratio of intracranial tumor to normal brain showed no change with dexamethasone, but the ratios of both intracranial and subcutaneous tumors to plasma significantly (P <0.002) decreased with both doses. The in vitro cell binding capacity of L6 IgG to LX-1 cells remained unchanged after incubation of cells with dexamethasone over a 3-log concentration for 4 days, demonstrating no effect on antigen expression. This study suggests that dexamethasone has a clinically relevant generalized (i.e., central nervous system and systemic) vascular effect on permeability to L6 IgG monoclonal antibody.

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