Paediatric neuroblastoma could be treated by nanocells
Biopharma company EnGeneIC has announced preclinical findings that highlight the potential of the company’s targeted, bacterially derived nanocells to enhance the delivery of intensive chemotherapy to tumours, while limiting toxicity to normal tissues, in aggressive paediatric malignancies, including neuroblastoma.
EnGeneIC’s EDV nanocells are able to package a variety of chemotherapeutic agents and target tumour cells via attachment of bispecific proteins to the nanocell surface. A Phase 1 clinical trial of epidermal growth factor receptor (EGFR)-targeted, doxorubicin-loaded EDVs in adults with recurrent glioblastoma showed that up to 8 x 109 nanocells given weekly was well tolerated, with no dose limiting toxicities or withdrawals due to adverse effects.
Following this trial, EnGeneIC and its collaborators sought to investigate this same treatment in paediatric neuroblastoma. The in vitro and in vivo studies, published in the journal Molecular Cancer Therapeutics, were conducted in collaboration with the Children’s Cancer Institute at the Lowy Cancer Research Centre, UNSW.
The two independent human neuroblastoma xenograft studies showed that treated mice exhibited a significant decrease in tumour size after 28 days, compared to non-treated mice and those treated with doxorubicin alone. This enhanced tumour shrinkage was also associated with a greater degree of apoptosis compared to the other groups. Moreover, median overall survival was significantly increased in nanocell-treated mice compared to groups treated with doxorubicin alone.
“We know doxorubicin works in killing cancer; however, the problem has always been getting the drug to the actual cancer cells while limiting its toxicity on healthy cells, which can cause short- and long-term side effects,” said Professor Maria Kavallaris, head of program, tumour biology and targeting at the Children’s Cancer Institute.
“These studies show that EnGeneIC’s nanocells can deliver drugs directly to the tumour, killing its cells.”
EnGeneIC is currently enrolling paediatric patients with advanced neurological tumours in a Phase 1 clinical study of EGFR-targeted, mitoxantrone-loaded EDVs at the Sydney Children’s Hospital and the Children’s Hospital Westmead. In addition, the company is currently evaluating its EGFR-targeted, doxorubicin-loaded EDVs in adults with recurrent glioma in a Phase 1 clinical study at two major US hospitals.
“Drug-loaded, bispecific antibody-targeted EDVs offer a highly promising approach for the treatment of aggressive paediatric malignancies,” EnGeneIC’s joint directors and CEOs, Dr Jennifer MacDiarmid and Dr Himanshu Brahmbhatt, said in a statement.
“In these studies, we demonstrated for the first time the ability of our bacterially-derived … delivery system to enter and kill neuroblastoma cells in vitro and in in vivo models of neuroblastoma. We look forward to continuing this work, which may lead to an improved standard of care for children with this devastating disease.”
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