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INTRACRANIAL ZIKA VIRUS INOCULATION IN A PATIENT WITH RECURRENT GLIOBLASTOMA: A BRIEF REPORT OF THE CLINICAL AND TECHNICAL ASPECTS IN A CASE OF COMPASSIONATE USE
Introduction, Objectives, Methods, Results, and Conclusion.
High-grade glioma is a primary malignant brain tumor with no current curative treatment. It is characterized by high rate of recurrence and limited survival, thus encouraging development of novel therapies. Treatments for the recurrence are limited and strategies with oncolytic viruses are under study in basic and clinical settings. Previous studies have shown that Zika virus (ZIKV) has in vitro potential for selective destruction of glial cells with stem cell properties, but there have been no reports of its use as a potential treatment paradigm in humans.
To report the development of a protocol – and its effects - for intracerebral inoculation of wild ZIKV in a 67-year-old female patient with recurrence of a left frontoparietal IDH wild-type glioblastoma, previously submitted to standard treatment.
Following confirmation of recurrence, the patient underwent surgery for tumor reduction and sampling. The tissue sample was cultured (DMEM-F12 + FBS 10%) and the cells inoculated with wild ZIKV. The viral particles were filtered and a solution of approximately 10*5 virions in 1,0 mL was injected in the surgical cavity and the ipsilateral ventricle. The intervention was proposed on a compassionate basis, overseen by the institutional ethics committee and legal department and for which consent was obtained from the patient and her family. Clinical, laboratorial and radiological assessments were performed whilst the patient was kept in an isolated infirmary ward for the first two weeks post-inoculation day (PID).
Oncolytic effects were observed in vitro following inoculation of the cultured tumoral cells. The patient presented clinical signs of Zika fever on the 9th PID; viral copies were detected in cerebrospinal fluid (CSF) and serum from the first to the 10th PID; NS1 protein was detected in the CSF from the third to the 14th PID and in serum from the 8th to the 10th PID. Serum IgM antibodies were detected from the 11th PID and IgG in CSF and serum from the 14th PID. Following tumoral resection, the patient presented with clinical improvement, which was sustained for the first five weeks post-injection. Unfortunately, the patient clinical status started deteriorating afterwards and she died 12 weeks after the inoculation.
The data presented here suggests that the use of ZIKV for the treatment of the recurrence of high-grade gliomas is feasible, thus warranting future investigation in clinical trials.
Keywords (separated by comma on a single line)
zika virus, glioblastoma, oncolytic viruses, viral therapy
GUILHERME GOZZOLI PODOLSKY-GONDIM, MARCUS VINICIUS GOMES DA SILVA, DANILLO LUCAS ALVES ESPOSITO, CARLOS GILBERTO CARLOTTI JR., FERNANDA MARIS PERIA, LUCIANO NEDER SERAFINI, ANTONIO CARLOS DOS SANTOS, CARLOS ALBERTO SCRIDELLI, LETICIA USSEM, BENEDICTO OSCAR COLLI, MARCUS VINICIUS DE CASTRO BARROS, FABIANO PINTO SAGGIORO, BENEDITO ANTONIO LOPES DA FONSECA