APA
Cloquell, Ana & Isidro, Mateo & Stefano, Gambera & Martí, Pumarola & Ramon, Alemany & García Castro, Javier & Perisé Barrios, Ana Judith .Systemic cellular viroimmunotherapy for canine high-grade gliomas.
ISO 690
Cloquell, Ana & Isidro, Mateo & Stefano, Gambera & Martí, Pumarola & Ramon, Alemany & García Castro, Javier & Perisé Barrios, Ana Judith. Systemic cellular viroimmunotherapy for canine high-grade gliomas.
https://hdl.handle.net/20.500.12080/33982
Resumen:
Background Oncolytic viruses constitute a growing field
of interest, both in human and veterinary oncology, given
that they are particularly helpful for treating non-surgical
tumors and disseminated cancer, such as high-grade
gliomas. Companion dogs present malignant gliomas
with biological, genetic, phenotypic, immunological, and
clinical similarities to human gliomas. These features
favor comparative approaches, leading to the treatment
of canine oncological patients to achieve translational
applications to the human clinic. The systemic
administration of oncolytic viruses presents a challenge
due to their limitations in effectively targeting tumors and
metastases. Therefore, the aim of this study is to evaluate
the safety and antitumor activity of a virotherapy used in
spontaneous canine tumors.
Methods Ten dogs with high-grade rostrotentorial
gliomas underwent weekly systemic endovenous cellular
virotherapy with dCelyvir (canine mesenchymal stem
cells infected with the canine oncolytic adenovirus
ICOCAV17) for 8 weeks. Efficacy was determined in
seven dogs according to the Response Assessment in
Veterinary Neuro-Oncology criteria considering clinical
status and MRI measurements. Medical history, physical
and neurological examinations, and vaccination status
were evaluated prior to and during follow-up. Safety was
evaluated by physical examinations and hematological
and biochemical changes in peripheral blood. Immune
populations were analyzed by flow cytometry in peripheral
blood and by gene expression and immunohistochemistry
in the tumor microenvironment.
Results The treatment was well tolerated and major
adverse effects were not observed. Two dogs had partial
responses (76% and 86% reduction in tumor size), and
3/7 showed stable disease. ICOCAV17 was detected in
peripheral blood in nine dogs, and a correlation between
the ICOCAV17 particles and anti-canine adenovirus (CAV)
antibodies was observed. ICOCAV17 was detected in
3/9 tumor tissues after necropsies. Regarding tumorinfiltrating lymphocytes, the dogs with disease stabilization
and partial response tended to have reduced memory
B-cell infiltration and increased monocyte/macrophage
lineage cells.
Conclusions These findings indicate that dCelyvir is safe
and presents efficacy in canine rostrotentorial high-grade
gliomas. These data are relevant to the ongoing phase Ib
regulated human clinical trial that is administering this
virotherapy to children, adolescents, and young adults with
diffuse pontine glioma. Celyvir should be further explored
as a treatment in veterinary and human neuro-oncology.