Correction to: Mast cell proliferation in the cerebrospinal fluid after intraventricular administration of anti‑B7H3 immunotherapy

AbstractOmburtamab is a B7H3-specific murine monoclonal antibody. B7H3 (CD 276) is a member of the B7 family of immune checkpoint co-inhibitory receptors overexpressed on many human malignancies. Radioimmunotherapy with 124I- or 131I-omburtamab administered in the cerebrospinal fluid (CSF), intraperitoneal or intratumoral cavity is currently under investigation for the treatment of CNS malignancies. The immunologic effects of anti-B7H3 therapy are not fully elucidated. A 6-year-old male was diagnosed with metastates of neuroblastoma to the received intraventricular 131I-omburtamab on an IRB-approved protocol. A treatment cycle consisted of a 2 mCi dosimetry dose and a 50 mCi treatment dose. Dosimetry by serial imaging, pharmacokinetics and safety were investigated. Clinical status, magnetic resonance imaging, CSF cell count and cytology were evaluated pre- and post-131I-omburtamab at 5 and 26 weeks. The patient did well with cycle 1. Three hours after the dosimetry dose of cycle 2, he developed a fever (39 °C), chills and headache. Blood and CSF samples were sent for culture. CSF was notable for nucleated cell pleocytosis with profound mast cell proliferation consistent with chemical meningitis. He was treated with supportive care; symptoms resolved over 48 h. Further therapy with 131I-omburtamab was electively discontinued. CSF cell count 5 weeks later demonstrated resolution of CSF pleocytosis. Local–regional administration of intraventricular 131I-omburtamab targeting B7H3 can result in a profound nucleated CSF pleocytosis with mastocytosis consistent with an acute allergic reaction.

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Faculty Opinions recommendation of KIT signaling regulates MITF expression through miRNAs in normal and malignant mast cell proliferation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.9549956.10205054 ◽

2011 ◽

Author(s):

Richard L Stevens

Keyword(s):

Cell Proliferation ◽

Mast Cell ◽

Mitf Expression

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Lung mast cell density and distribution in chronically hypoxic animals

Journal of Applied Physiology ◽

10.1152/jappl.1977.42.2.174 ◽

1977 ◽

Vol 42 (2) ◽

pp. 174-178 ◽

Cited By ~ 28

Author(s):

A. Tucker ◽

I. F. McMurtry ◽

A. F. Alexander ◽

J. T. Reeves ◽

R. F. Grover

Keyword(s):

Cell Proliferation ◽

Pulmonary Hypertension ◽

Mast Cell ◽

Mast Cells ◽

Cell Density ◽

Mammalian Species ◽

Cell Hyperplasia ◽

Mast Cell Density ◽

Lung Mast Cell ◽

Mast Cell Hyperplasia

Changes in the density and distribution of pulmonary mast cells were determined in six mammalian species exposed to hypobaric hypoxia (PB = 435 Torr) for 19–48 days. Control animals were studied at 1,600 m (PB = 635 Torr). Total lung mast cell hyperplasia was observed only in calves exposed to high altitude. Pigs, rats, and sheep exhibited small, but insignificant, increases in mast cell density. Perivascular mast cell proliferation adjacent to vessels of 30–500 mum in diameter was seen in both calves and pigs. Bronchial, alveolar septal, and systemic tissue (tongue) mast cell hyperplasia was not observed in any of the species. Three indices of pulmonary hypertension (right ventricular hypertrophy, medial thickness of pulmonary arteries, and pulmonary arterial pressure) correlated with perivascular mast cell density. The findings indicate that perivascular mast cell proliferation may relate more to the morphological pulmonary vascular changes and to pulmonary hypertension than to hypoxia, leading to the speculation that mast cells increase in number in response to the hypertension, rather than to mediate and maintain the hypertension.

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