Why cell therapies?
Until recently, cancer drugs have largely been chemical and/or biological (e.g. antibodies) in nature ─ discovered, developed and/or synthesized in laboratories. Chemical-based therapeutics generally act on all cells they encounter and are developed because they have greater activity on cancer cells than normal cells in our bodies. Biological therapies are more targeted in nature, but are less potent at killing cancer cells. While antibody-drug conjugates, or ADCs, combine properties of chemical- and biologic-based therapies, these drugs exist in our bodies only for a short period of time after injection, often requiring multiple treatments to shrink tumors.
Cell therapies are comprised of harvesting immune cells from our body, engineering them to recognize specific tumor antigens, and then re-injecting them back into our bodies to seek and destroy tumor cells expressing the tumor antigen of interest. Cell therapies leverage the natural ability of immune cells to be activated, for example, only when they encounter specific target proteins, after which they can replicate and expand in numbers to overwhelm and eradicate tumors. Cell therapies can also persist in our bodies for long periods of time (weeks and months) and can continue to surveil for cancer cells long after treatment has been administered. As a result, cell therapies do not require patients to keep visiting their doctor to receive additional treatments.
Critical challenges exist to improving the efficacy and safety of cell therapies
Most tumors have developed defense mechanisms in their local environment, which suppress the immune system and prevent conventional cell therapies from working. Conventional cell therapies are programmed with synthetic, unoptimized code, often leading to poorly controlled behavior (e.g. too much protein expression) that results in exhaustion or loss of the cell therapy over time. Cell therapies are also extremely potent due to their ability to replicate. If these cells or the proteins they’re making are not finely controlled, severe toxicities can result.
How Chimera’s technology can enable safer, more effective cell therapies
By endowing cell therapies with the ability to produce “payloads” (i.e. proteins intended to help cell therapy function) only when they encounter tumor cells, these therapies can be engineered to counteract an immunosuppressive tumor microenvironment and/or increase T-cell expansion to improve their ability to find and kill tumor cells. By also designing and optimizing protein expression using natural control code already used by cells in our body, our engineered cell therapies can operate in balance with the body to eliminate disease when patients are ill and exist in equilibrium for long periods of time when the body is healthy. By controlling the where, when and how much payload is produced as our engineered cell therapies find tumor cells, we avoid systemic expression of proteins that can be helpful to the T-cells in tumors but be harmful if present elsewhere in the body.
Above Image: Seung-Young Lee, S. (2015, July 1). Spatial Heterogeneity in the Tumor Microenvironment: NCI. National Cancer Institute.
A cancer diagnosis is hard enough; we are striving to create a treatment with dignity and humanity.
T-cells are one of the primary executors of immune responses against cancer. When our immune system is effective at recognizing and killing cancer cells, we go about our daily lives unaware that abnormal cells arose and were eliminated. When cancer cells get the upper hand over the immune system, they grow into masses that are eventually detected and diagnosed. When many tumor types are initially diagnosed, especially those of the solid tumor variety, they are often too advanced to cure. Furthermore, many of the limited available therapeutic options rob patients of their health and dignity.
Our mission is to improve the efficacy and safety of engineered cell therapies with the goal of transforming the promise of this new therapeutic class into a reality that offers the hope of cures for cancer patients with currently incurable tumor types.
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