Tocagen Inc (TOCA)

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Good observations for direct injection: A surgeon injects the virus into the site of highest tumor concentration in the brain. Later, the patient is given oral, extendedrelease 5-fluorocytosine, which the CD gene converts into 5-fluorouracil, activating the immune system against cancer. Other engineered viruses work by inserting RNA rather than DNA into cancer cells.

It was initially thought that oncolytic viruses killed just the cancer cells into which they were injected, but Masahiro Toda, M.D., Ph.D., and colleagues demonstrated that the technique acts systemically, shrinking tumors that are both at and distant from the injection site. This could play a critical role in generating durable responses in patients with metastatic or aggressive disease.

Rabkin and Howard L. Kaufman, M.D., chief medical officer of the biotechnology company Replimune, agreed that, because of new techniques in interventional radiology and minor surgery, direct injection of the virus is possible for most tumors and would be more effective than IV administration, which tends to kick off an immune response against the drug. “With modern neurosurgical techniques, almost all areas (of the brain) are accessible to biopsy,” Rabkin said. “If you can perform a biopsy, you can deliver the virus.”

https://www.curetoday.com/publications/cure/2018/immunotherapy-special-issue/contagious-enthusiasm