Despite the many oncolytic viruses in clinical trials as treatments for cancer, most of them suffer from a debilitating flaw. “The unprotected oncolytic viruses used in the past were quickly eliminated by the patient’s immune system, leading to a limited therapeutic potential,” says Boris Minev, MD, who is president, medical & scientific affairs at Calidi Biotherapeutics in San Diego. So, this company protects the virus.
“Our approach is a Trojan Horse strategy that utilizes stem cells to protect the oncolytic viruses from inactivation by the body’s immune system,” Minev explains. “This allows the virus to begin replication and gene expression inside the stem cells before it’s delivered, effectively transforming the tumor microenvironment and inducing an anti-tumor response upon delivery.”
As one example of Calidi’s approach in a recent Phase I clinical trial, neural stem cells loaded with an oncolytic adenovirus established “the safety and signals of efficacy in patients with newly diagnosed glioblastoma,” Minev says.
This technique, though, can be applied to a wide range of cancers. Calidi is also working on treatments for breast cancer, melanoma, and squamous-cell head and neck cancers.
In bioprocessing, Calidi faces several challenges: expanding the virus and the stem cells, and then controlling efficient virus-loading processes. As Minev notes: “Stem cells loaded with oncolytic viruses are manufactured as a single vial.”
Despite the challenges of controlling so many bioprocesses, it pays off. As Minev says, “The combined effect of efficient cell-based delivery and potentiation of virus, direct eradication of cancer cells by the oncolytic viruses, and induction of anti-tumor immunity are responsible for the potent anti-tumor efficacy of this approach, not only at the injected tumor site but also at distant metastatic tumor sites.”
Creating cell-based cancer therapies always comes with challenges in bioprocessing. The future of such therapies, however, could raise the complexity of bioprocessing even more. Nonetheless, meeting that challenge could produce far more effective cancer treatments.
