SAN DIEGO, June 19, 2017 /PRNewswire/ -- Tocagen Inc.
(Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy
company, today announced the publication of preclinical data in
Neuro-Oncology from two independent research programs which
together detail proposed mechanisms of action for Toca 511 &
Toca FC involving direct tumor killing and activation of the immune
system against cancer cells. The papers were published in the July
issue of Neuro-Oncology, which appeared in print on
June 16, 2017, and were featured on
the cover and highlighted in an editorial. The articles first
appeared online on April 6, 2017.
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 Noriyuki Kasahara,
M.D., Ph.D., professor of cell biology and pathology at the
University of Miami. While long-term
survival benefit was seen in both models, tumor was undetectable in
immune-competent mice after three cycles of 5-FC. In contrast,
immune-deficient mice required continuous treatment with cycles of
5-FC for long-term survival benefit, and tumor recurrence was still
evident between cycles. After clearance of tumors in
immune-competent mice by treatment with Toca 511 and 5-FC,
long-term protection against future challenge with the same tumor
type was seen. Long-term immune memory against the tumor was lost
upon depletion of T cell subsets, indicating a T cell-dependent
anti-tumor immune response.
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. Tocagen has completed enrollment of the Phase 2 portion of
a Phase 2/3 clinical trial and plans to report top-line results of
the study in the first half of 2018. The U.S. Food and Drug
Administration (FDA) granted Toca 511 & Toca FC Breakthrough
Therapy Designation for the treatment of patients with recurrent
HGG.
Research reported in the publication by Hiraoka and Inagaki, et
al. was supported in part by the National Institute of Neurological
Diseases and Stroke (NINDS) in the National Institutes of Health
(NIH) under award number U01NS059821. The content is solely the
responsibility of the authors and does not necessarily represent
the official views of NINDS or NIH.
About Tocagen
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 (FDA) for the treatment of recurrent
HGG. Tocagen has received grant support from leading
brain cancer foundations, including Accelerate Brain
Cancer Cure (ABC2), National Brain Tumor
Society (NBTS), American Brain Tumor
Association (ABTA), Musella Foundation and Voices
Against Brain Cancer (VABC). For more information,
visit www.tocagen.com or follow @Tocagen.
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/complementary-preclinical-studies-published-in-neuro-oncology-demonstrate-immune-activation-mechanism-of-tocagens-toca-511--toca-fc-300475525.html
SOURCE Tocagen Inc.