How CTLs Work in the Body

Human leukocyte antigens (HLAs) are a group of normal proteins that play an important role in the way the immune system works. There are many different types of HLA proteins, some of which are found on the surface of nearly every cell in your body, and each person has a characteristic combination of HLAs that contribute to their individual immune profile (also called an HLA genotype). One of the important functions of HLA proteins is that they present disease-related antigens to T-cells of the immune system. Each T-cell has a specific target antigen it is able to recognize, and it can only do so when its target antigen is presented by (i.e. connected to) an HLA protein. The HLA protein through which a CTL recognizes it’s target antigen and eliminates a diseased cell is known as it’s HLA restriction.

Atara’s CTL library is composed of fully HLA-characterized CTL lines, with a breadth of HLA profiles and HLA restrictions. When a patient is in need of treatment, our proprietary CTL selection algorithm identifies the most appropriate CTL line matched to the patient’s HLA genotype. Once the line is selected:

  1. The CTLs are thawed and administered intravenously over about 5 minutes in an outpatient or inpatient setting,
  2. The administered CTLs circulate throughout the body, ignoring healthy cells that don’t express the target antigen, and very specifically identifying diseased cells that do express the antigen,
  3. CTLs eliminate diseased cells when they recognize the target antigen connected to their particular HLA restriction, and
  4. CTLs also undergo target-controlled proliferation. This means they expand in number as long as they encounter the target antigen. Once they no longer encounter the target antigen, proliferation of the CTLs stops and their numbers recede.