Posted on 03/14/2023 9:16:14 AM PDT by ConservativeMind
A type of immune therapy called chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of multiple types of blood cancers but has shown limited efficacy against glioblastoma and other solid tumors.
New research suggests that drugs that correct abnormalities in a solid tumor's blood vessels can improve the delivery and function of CAR-T cell therapy.
With CAR-T cell therapy, immune cells are taken from a patient's blood and are modified in the lab.
"One of the main reasons that CAR-T therapy hasn't worked well against solid tumors is that intravenously administered cells are only capable of migrating to either the invasive edges of a tumor or only in limited areas of the tumor," says Rakesh K. Jain, Ph.D.
"Also, tumors create an environment around them that is immunosuppressive, that protects them from CAR-T therapy and other anti-cancer treatments administered intravenously through the blood supply."
Jain and his colleagues previously showed that "normalizing" tumor's blood vessels with agents called anti-angiogenesis drugs, originally developed to inhibit the growth of new blood vessels, can improve the delivery and anti-cancer function of immune cells naturally produced by the body.
"Therefore, we sought to investigate if we could improve CAR-T cell infiltration and overcome resistance mechanisms posed by the abnormal tumor microenvironment by normalizing glioblastoma blood vessels using an antibody that blocks an important angiogenic molecule called vascular endothelial growth factor, or VEGF," Jain explains.
The team found that treatment with an antibody against VEGF improved the infiltration of CAR-T cells into glioblastoma tumors in mice. The treatment also inhibited tumor growth and prolonged survival in mice with glioblastoma.
"Given that an anti-VEGF antibody—bevacizumab—has been approved for glioblastoma patients and that there are several CAR-T therapies being tested in patients, our results provide a compelling rationale for testing the combination," says Jain.
(Excerpt) Read more at medicalxpress.com ...
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