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Heat
reports ComPACT therapy data
May 2017
EDIT CONNECT
SHARING OPTIONS:
DURHAM, N.C.—Heat Biologics Inc. recently presented new preclinical data from its collaboration with OncoSec Medical Inc., focused on evaluating the combination of Heat’s immunotherapy platforms with
intratumoral electroporation (EP), at the American Association for Cancer Research (AACR) Annual
Meeting with a poster entitled “Combined Intratumoral Electroporation and Allogenic Vaccination of Gp96-Ig/Fc-OX40L Stimulates CD8+ T cell Cross
Priming to Tumor-Specific Neoantigens and Enhances Anti-Tumor Response.”
Data from the poster demonstrated the effects
of an intratumoral plus vaccination approach in a preclinical mouse model of melanoma. Researchers combined EP of ComPACT DNA (expressing gp96-Ig and Fc-
OX40L) directly into a tumor, with the cell-based Combination Pan-Antigen Cytotoxic Therapy, or ComPACT, to test possible synergistic benefits of vaccination
plus intratumoral injection versus separate administration of vaccine and OX40 agonist antibody. The results presented confirmed that this combination
approach led to increased antigen-specific CD8+ T cells, enhanced antitumor response and improved overall survival compared to individual treatments.
Heat Biologics’ highly specific T cell-stimulating therapeutic vaccine platform technologies—ImPACT and
ComPACT—in combination with other therapies, such as checkpoint inhibitors, are designed to address three distinct but synergistic mechanisms of
action: robust activation of CD8+ killer T cells, one of the human immune system’s most potent weapons against cancer; reversal of tumor-induced immune
suppression; and T cell co-stimulation to further enhance patients’ immune response. Their goal is to implement this therapy in the simplest and most
efficacious way possible and with the lowest possible toxicity.
Heat’s approach is an off-the-shelf product
that does not require invasive surgery or the isolation of patient tissues, as is required for autologous vaccine technologies. The company’s Immune
Pan-Antigen Cytotoxic Therapy, or ImPACT, is an engineered cell line designed to express a version of a naturally occurring heat-shock protein known as gp96,
transforming allogenic living cancer cells into powerful miniature osmotic pumps that continually secrete heat shock protein gp96 along with its chaperoned
antigens. The protein gp96 is a “molecular warning system” that has evolved important properties as a natural defense against necrotic cell
death, in order to alert the immune systems to the presence and identity of dangerous pathogens. By developing cell lines to secrete an engineered form of
gp96, this technology simulates the immune system’s natural abilities.
Clinical and preclinical results
indicate that ImPACT Therapy generates a potent antitumor immune response that fights targeted tumors and keeps the body tumor-free even when re-challenged
with the cancer. This novel live-cell vaccine approach is applicable to a wide array of viral infections, including HIV and HCV, and parasitic infections
like malaria as well as cancer.
The CD8+ cytotoxic T cell specific nature of the ImPACT system predicts that it
will be most useful in stimulating immune responses for diseases where actual cell-killing is an important part of the therapeutic effect. Cancer, which is a
disease of mutated cells, naturally became the first indication. ImPACT applied to cancer therapy contrasts in several critical ways to other cancer
immunotherapy technologies.
Taking this technology a step further, ComPACT enables Heat to combine a pan-antigen T
cell-activating vaccine and a T cell co-stimulator in a single product, offering the potential benefits of combination immunotherapy without the need for
multiple independent biologic products. Using ComPACT, the company has engineered new product candidates that incorporate various ligand fusion proteins
targeting co-stimulatory receptors (OX40, ICOS, 4-1BB) into the gp96-Ig expression vector, resulting in a single product candidate that includes both a pan-
antigen T cell-priming vaccine and a T cell co-stimulator.
Heat is exploring various co-stimulatory receptors that
may synergize with gp96-Ig-based vaccines. Findings from studies using the ImPACT vaccine demonstrate that antibodies quickly distribute systemically and
produce systemic effects, while ComPACT vaccine research shows a local secretion of Fc-OX40L, producing superior antigen-specific CD8+ T cells associated
with an increase in memory precursor cells. Studies have showed improved survival in a mouse colon cancer model.
Heat is currently in the midst of a Phase 2 trial with HS-110 (viagenpumatucel-L) in combination with an anti-PD-1 checkpoint inhibitor to treat
patients with non-small cell lung cancer and a Phase 2 trial with HS-410 (vesigenurtacel-L) in patients with non-muscle invasive bladder cancer. In addition,
Heat’s wholly owned subsidiary, Zolovax Inc., is developing therapeutic and preventative vaccines to treat infectious diseases based on Heat’s
gp96 vaccine technology, with a current focus on the development of a Zika vaccine in conjunction with the University of Miami.
“This proof-of-principal study shows there may be benefit in combining our vaccines with an intratumoral approach to
deliver the vaccine directly into the tumor to increase the coverage of tumor-specific shared antigens and neo antigen presentation,” said Dr. Jeff
Hutchins, Heat’s chief scientific officer and senior vice president of preclinical development. “It opens up the possibility of pairing our
ImPACT and ComPACT platform technologies with intratumoral approaches, which aligns with our strategy to advance new, synergistic immuno-oncology
combinations to improve patient outcomes.”
Code: E051712 Back |
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