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|Complementary Preclinical Studies Published in Neuro-Oncology Demonstrate Immune Activation Mechanism of Tocagen's Toca 511 & Toca FC|
In the article titled, "Toca 511 gene transfer and treatment with the prodrug, 5-fluorocytosine, promotes durable anti-tumor immunity in a mouse glioma model," Mitchell, et al., monitored and characterized immune cell populations in the tumor microenvironment in mouse models of brain cancer over the course of treatment with Toca 511 and 5-FC, the active component of the Toca FC tablets used in humans. Results showed treatment-induced loss of immune cell subsets that have been shown to contribute to the suppression of normal immune activity against cancer cells, including reduction of tumor associated macrophages, myeloid-derived suppressor cells and tumor associated monocytes. Depletion of immune-suppressive myeloid cells was followed by increases in CD4+ and CD8+ T cells which correlated with tumor reduction. Mice that cleared tumors following treatment with Toca 511 and 5-FC were protected against re-challenge with the same tumor type. Furthermore, successful adoptive cell transfer experiments using isolated immune cells from successfully treated animals confirmed anti-tumor immune responses were T cell-dependent.
In the article titled, "Retroviral replicating vector-mediated gene therapy achieves long-term control of tumor recurrence and leads to durable anti-cancer immunity," Hiraoka and Inagaki, et al., performed molecular imaging of immune-deficient and immune-competent mouse models of brain cancer following treatment with Toca 511 and cycles of 5-FC. These studies were performed in the laboratory of
The complementary findings reported in these publications demonstrate that anti-tumor immune effects are T-cell dependent and correlate with depletion of immune-suppressive myeloid cells.
Toca 511 & Toca FC is in clinical development for the treatment of recurrent high grade glioma, or HGG, a type of brain cancer.
Research reported in the publication by Hiraoka and Inagaki, et al. was supported in part by the
Tocagen is a clinical-stage, cancer-selective gene therapy company developing first-in-class, broadly applicable product candidates designed to activate a patient's immune system against their own cancer. Tocagen is developing its lead investigational product candidate, Toca 511 & Toca FC, initially for the treatment of recurrent high grade glioma (HGG), a disease with significant unmet medical need. Toca 511 & Toca FC was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (
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