Atara Biotherapeutics’ allogeneic cytotoxic T lymphocyte (CTL) immunotherapy platform is based on the precision of our CTLs to specifically recognize and then target antigens expressed by cancerous or diseased cells. This allows the CTLs to eliminate diseased cells without affecting normal, healthy ones.
CTL Scientific Overview
The T lymphocyte is a type of white blood cell that performs several important functions in a healthy immune system. Cytotoxic T lymphocytes (CTL) are a subset of T lymphocytes that have the specialized ability to detect and kill abnormal or diseased cells in the body. In patients with cancer and certain autoimmune conditions, the patient’s T lymphocytes are unable to effectively eliminate diseased cells due to a combination of: an inability to recognize the abnormal cells, an inability to function correctly to kill the abnormal cells, and/or insufficient numbers of T lymphocytes.
Atara Biotherapeutics’ allogeneic CTL technology is designed to harness, augment, and then transfer targeted, healthy T-cell immunity to a patient suffering from cancer, certain autoimmune diseases, or serious viral infections.
There are several important aspects of the technology.
Our T-cells are derived from healthy donors which means that we start with cells that have healthy immune function. We then apply our technology platforms to create T-cell lines that are precision-targeted to treat specific conditions (see below for more details on precision targeting). The advantages to this approach include:
- Off-the-shelf, ready-to-utilize therapeutic CTL lines through a pre-built library of inventory. For our lead program ATA129, a relatively small number of lines is able to cover the majority of the population
- Efficient management of therapeutic inventory
- Prompt treatment – from the identification of need, we can deliver a therapeutic T-cell line for a patient in ~ 3-5 days
Compelling safety profile
- No lymphodepletion required before treatment
- For ATA129, in 126 patients treated there were:
- Nine possibly related serious adverse events, or SAEs
- No infusion related toxicities
- No evidence of cytokine release syndrome
- One case of treatment-related grade 1 graft versus host disease, or GvHD, which resolved with topical treatment
CTL selection algorithm
Our CTL selection algorithm was developed through over a decade of clinical experience at Memorial Sloan Kettering (MSK) treating a variety of cancers and infections. The algorithm identifies the most appropriate CTL lines in our library for any individual patient, based on matching certain key immune characteristics of the CTL lines to the unique immune profile of each patient.
Our CTL immunotherapy platform currently comprises two complimentary technologies we utilize to specifically target the CTLs for treating different diseases:
- Our core technology, licensed from MSK, creates CTLs broadly targeted to recognize EBV and CMV viral antigens, and the tumor associated antigen, Wilms tumor 1 (WT1). This technology is being applied to development programs for treating hematologic tumors, solid tumors (e.g. nasopharyngeal carcinoma), and severe infectious diseases. The specific product candidates developed using this technology are ATA129, ATA230, and ATA520
- Our next generation CTL technology, licensed from QIMR Berghofer, uses selective antigen targeting to create CTLs targeted for specific EBV, CMV, HPV, and BK viral antigens that may be important in certain diseases. This selective antigen targeting is being utilized for development programs in certain solid tumors (e.g. gastric cancer) and autoimmune conditions (e.g. multiple sclerosis). The specific product candidates using this technology are ATA188, ATA621, ATA368, and ATA274