ATA520 is an immunotherapy being developed by Atara Biotherapeutics as a potential treatment for hematologic malignancies, or cancers of the blood including multiple myeloma (MM) and plasma cell leukemia (PCL).
The treatment aims to activate cytotoxic T-lymphocytes (CTLs), a subset of specialized T-cells that have the ability to detect and kill abnormal or diseased cells in the body. However, in patients with cancer, T-cells are unable to effectively eliminate diseased cells.
How ATA520 works
ATA520 is produced using T-cells derived from healthy donors that have normal immune function capacity. The treatment is specifically targeted against the tumor-associated antigen Wilms tumor 1 (WT1), an intracellular protein that is overproduced in a number of cancers including MM, non-small cell lung cancer (NSCLC), breast cancer, pancreatic cancer, ovarian cancer, and colorectal cancer.
Upon administration into the bloodstream, ATA520 circulates throughout the body, ignoring healthy cells that do not express the target antigen WT1 and specifically identifying and destroying diseased cells that do.
CTLs also undergo target-controlled proliferation. This means that they expand in number as long as they encounter the target antigen. Once they no longer encounter the target antigen — when the tumor cells have all been destroyed— the proliferation of the CTLs stops and their numbers decrease.
ATA520 in clinical trials
ATA520 is being evaluated in two ongoing Phase 1 clinical trials in the U.S.
The first is a dose escalation trial (NCT00620633) designed to test the safety of ATA520 in 22 patients with residual or relapsed leukemia after allogeneic hematopoietic progenitor cell transplantation (HCT), also known as allogeneic stem cell transplant. The study is expected to be completed by 2018.
The second trial is also a dose-escalation study (NCT01758328), but following T-cell depleted HCT in patients with relapsed or refractory (drug-resistant) MM, including PCL.
Preliminary results from this trial were presented at the 43rd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT). Patients with relapsed-refractory MM, including PCL, were treated with allogeneic HCT followed by WT1-CTLs, and at one year, a response rate of greater than 50% was observed in the patients. Two patients who developed a complete response remained in remission for more than one year. There were no serious adverse effects related to the treatment.
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