Our proprietary, ImPACT® and ComPACTTM T-cell Activation Platform (TCAP) technologies produce allogeneic, “off-the-shelf” therapies that stimulate a patient’s immune system to attack and destroy cancer cells.
ImPACT and ComPACT are based on the development of an engineered form of the heat shock protein, gp96. gp96 is a “molecular warning system” that has evolved important properties as a natural defense against necrotic cell death, in order to serve as a sentinel to alert the immune system to the presence and identity of dangerous pathogens. By developing cell lines to secrete an engineered form of gp96, Heat’s ImPACT technology is able to simulate a process that our immune systems have naturally evolved over millions of years.
“I formed Heat with the singular goal of developing innovative and powerful tools to harness the body’s natural immune system to treat cancer. My father died of cancer, but it wasn’t the cancer that killed him. It was the toxic effect of the chemotherapy that destroyed his body, will and life. Heat strives to offer a less toxic, more effective approach to treating patients with cancer.
“As immunotherapy transforms the treatment of cancer, it has become clear that combining strategies to stimulate a targeted T-cell immune response with those that overcome tumor defenses will provide the most durable patient benefit. We’ve worked hard to assemble a portfolio of technologies to activate T-cells, a critical component of any immunotherapy cocktail.”
– Jeffrey Wolf, Heat Biologics CEO
Our Immune Pan-antigen Cytotoxic Therapy (ImPACT®) platform is a cell-based therapy that drives the immune system to attack and destroy tumors.
It is a T-cell-stimulating platform, and along with our ComPACT™ technology, form the basis of our product candidates. ImPACT has two responsibilities:
- Functions as an immune activator to stimulate T-cells
- Acts as a delivery vehicle for modified cancer cells injected into the body during treatment
ImPACT reprograms a live, genetically modified cancer cell line and binds it to the heat-shock protein, gp96. Once the cell line is injected into the body along with a checkpoint inhibitor, they are able to continually secrete their own mutated antigens bound to gp96.
The cells live in the body for days. As the immune system begins to recognize the antigens attached to gp96, the checkpoint inhibitor kicks in, triggering an immune response to activate “killer” T-cells. Killer T-cells seek out and attack the cancer cells, essentially causing the tumor to destroy itself.
This combination approach has been shown to induce and maintain an immune response against multiple tumor proteins, and keeps the body tumor-free, even when re-challenged with the cancer.
Our Combination Pan-antigen Cytotoxic Therapy (ComPACT™) takes advantage of all aspects of the T-cell activation platform, ImPACT®, and builds upon them.
ComPACT helps unlock the body’s natural defenses and provides the added benefit of co-stimulation to enhance T-cell activation and expansion. It has the potential to simplify combination immunotherapy development for oncology patients, as it’s designed to deliver the gp96 heat shock protein and a T-cell co-stimulatory fusion protein (OX40L) into a single compound.
ComPACT offers the potential benefits of combination immunotherapy without the need for multiple, independent biologic products.
- Enhances activation of antigen-specific CD8+ T-cells
- Serves as a booster to expand the number of antigen-specific T cells compared to OX40 alone
- Stimulates cell memory function to remain effective in the body after treatment, even if the cancer comes back
- Demonstrates less toxicity since the unique identifier and co-stimulatory are supplied at the same time, driving targeted immunity towards the tumor rather than throughout the body
The heat shock protein, gp96, acts as an adjuvant, or immune stimulator, that simultaneously boosts the immune system and notifies it of harmful pathogens.
Gp96 is a molecule present in all human cells, and its job is to interact with proteins to trigger an immune response against antigens.
- It is typically found within the cell’s endoplasmic reticulum, and facilitates the folding of newly synthesized proteins so they can properly perform their various tasks. However, when a cell abnormally dies through necrosis or disease, gp96 is released into the surrounding tissues, damaging other cells.
The building blocks of our immuno-oncology platforms, ImPACT® and ComPACT™, are formed through an engineered form of the gp96 heat shock protein.
- It helps to stimulate a patient’s immune system and alert it to the presence of harmful pathogens; and then activates a T-cell response against tumors associated with the cancer.
- Our therapy reprograms live tumor cells to continually secrete gp96 into the body, along with their chaperoned tumor antigens, without causing necrosis. The cells are then transformed into machines that activate an immune attack, and seek out to destroy antigens before the body would otherwise have detected them.
What is a Heat Shock Protein?
Heat shock proteins (HSPs) are common in the body, and play a role in assembling and transporting proteins between cell compartments, and repairing misfolded proteins during times of stress. They have proven to be effective at preventing cancer development and growth. As the body’s immune response stimulator, gp96 assists Heat’s therapies in tumor rejection by delivering multiple, mutated tumor proteins to immune cells.