Heat shock proteins: basics

What are heat shock proteins and how do they work?

Heat shock proteins (HSPs), also called stress proteins, are a group of proteins that are present in all cells in all life forms. They are induced when a cell undergoes various types of environmental stresses like heat, cold and oxygen deprivation.

Heat shock proteins are also present in cells under perfectly normal conditions. They act like ‘chaperones,’ making sure that the cell’s proteins are in the right shape and in the right place at the right time. For example, HSPs help new or distorted proteins fold into shape, which is essential for their function. They also shuttle proteins from one compartment to another inside the cell, and transport old proteins to ‘garbage disposals’ inside the cell. Heat shock proteins are also believed to play a role in the presentation of pieces of proteins (or peptides) on the cell surface to help the immune system recognize diseased cells.

Learn more about our investigational products based on HSP technology:

Oncophage for cancer

AG-707 for genital herpes

What do heat shock proteins have to do with cancer?

For decades it has been known that animals can be ‘vaccinated’ against cancer. This is how it works: Tumor cells can be weakened, or attenuated, and injected like a vaccine into a mouse. Afterwards, if these same tumor cells, at full strength, are injected into the mouse, the mouse will reject the tumor cells and cancer will not develop. However, if a mouse has not been vaccinated in this manner, the tumor cells will ‘take’ and the mouse will develop cancer.

Although it was clear that animals could be vaccinated against cancer, for a long time it was not known how it worked. Then about 25 years ago, a graduate student named Pramod Srivastava began a series of experiments. He took tumor cells, broke them open, and separated the different parts of the cells into fractions. He then used each of the fractions as ‘vaccines’ to see which fraction protected the mice from developing cancer. After many experiments, he found that the element responsible for protecting the mice was heat shock proteins. [More]

How are heat shock proteins involved in generating immune response?

Heat shock proteins trigger immune response through activities that occur both inside the cell (intracellular) and outside the cell (extracellular).

Intracellular activities

Because of the normal functions of heat shock proteins inside the cell (such as helping proteins fold, preparing proteins for disposal, etc.), HSPs end up binding virtually every protein made within the cell. This means that at any given time, HSPs can be found inside the cell bound to a wide array of peptides that represent a ‘library’ of all the proteins inside the cell. This library contains normal peptides that are found in all cells as well as abnormal peptides that are only found in sick cells.

Journals in which HSP research has been published

Research suggests that inside the cell, heat shock proteins take the peptides and hand them over to another group of molecules. These other molecules take the abnormal peptides that are found only in sick cells and move them from inside the cell to outside on the cell’s surface. When the abnormal peptides are displayed in this way, they act as red flags, warning the immune system that the cell has become sick. These abnormal peptides are called antigens — a term that describes any substance capable of triggering an immune response.

Extracellular activities

Heat shock proteins are normally found inside cells. When they are found outside the cell, it indicates that a cell has become so sick that it has died and spilled out all of its contents. This kind of messy, unplanned death is called necrosis, and only occurs when something is very wrong with the cell. Extracellular HSPs are one of the most powerful ways of sending a ‘danger signal’ to the immune system in order to generate a response that can help to get rid of an infection or disease. [More]

How does Antigenics’ heat shock protein technology work?

Antigenics’ heat shock protein technology works by mimicking the ‘danger signal’ believed to be naturally triggered by extracellular HSPs. Depending on the abnormal peptides contained within the HSP-associated ‘library’ of proteins that have spilled out of the cell, the immune system can be activated to target different cancers and certain infectious agents.

Antigenics’ investigational patient-specific cancer vaccine Oncophage^® (vitespen; formerly HSPPC-96) consists of HSP-peptide complexes that have been isolated from individual patient’s cancer cells. Because cancer is so incredibly variable, the abnormal peptides found within diseased cells are different from cancer to cancer and from person to person. Therefore, this library of abnormal peptides is unique to each individual’s disease and can be thought of as the cancer’s ‘fingerprint.’

When the vaccine is injected into the body, the fingerprint of HSP-peptide complexes can directly encounter the immune system’s cells, which is designed to stimulate the immune cells to target cancer cells bearing this fingerprint. [More]

Read our white paper on heat shock proteins.