Antibodies are specialized proteins produced by B cells, a type of immune cell, in response to pathogens or disease antigens. Through their ability to bind selectively and tightly to disease antigens and through their ability to elicit further responses from immune cells, they can neutralize foreign objects such as bacteria, viruses or other diseased cells. Antibodies have become a popular therapeutic category because they have enabled the development of new drugs against targets not possible with small molecule chemistry, have high specificities for their targets, enable infrequent dosing and can lead to fewer side effects.
Despite growth in the market for antibody drugs, those targeting immune checkpoint proteins may serve an area of considerable unmet medical need. Immune checkpoints are proteins on immune cells that coordinate and regulate appropriate immune responses but can become dysregulated in disease.
The human immune system uses checkpoint proteins as “breaks” to prevent runaway immune activity, which can prove to be debilitating or even deadly. Although checkpoint proteins usually function appropriately to regulate immune responses, cancers can impact their function, which can leave tumors unchecked by the immune system. For example, mechanisms of checkpoint proteins can hinder a natural immune response to cancers or other diseased cells, or cancer cells themselves can sabotage the function of these mechanisms as a defense against an immune response.
Immunomodulatory antibodies (immunotherapy) bind to protein antigens expressed on the immune cells of patients, rather than to pathogens or diseased cells. Such antibodies that bind to checkpoint proteins either enhance or block specific checkpoint processes. Though poorly understood in humans, it is widely believed that through such host immune cell binding changes in the behavior of immune cells are elicited that help to control the disease process. With these proteins modulated, cancers may be more susceptible to destruction by the body’s immune responses.
A full understanding of the myriad cell types, disease situations and human variability, where immune checkpoints are expressed, and exactly how and when they function, is not currently known. A key bottleneck in the field is limited understanding of human patient immunology at the level of human cells to guide validation and development of best-in-class therapies that effectively target the right patients. Enumeral’s human cell-based evaluation methods along with our unique antibody screening capabilities may provide us with a distinct competitive advantage in the development of immunotherapies.