The company is exploring the potential of ALT-803 in combination with other immunotherapies to further boost the immune response.
How ALT-803 works
NHL is the most common type of lymphoma. The disease originates in the B or T-cells, which are immune system cells responsible for combating infections or threats against the body.
Another type of immune system cells is natural killer (NK) cells. These constitute the body’s first line of defense and have the innate ability to rapidly seek and destroy abnormal cells, like cancer cells, without requiring prior exposure or activation by support molecules.
NK cells express a number of cytokine receptors (proteins) necessary for their functions, including the receptor for the interleukin-15 (IL-15) protein. IL-15 is a naturally-occurring molecule in the body that is critical for the activation and proliferation of NK cells. IL-15 also enhances the anti-tumor activity of cytotoxic T-cells, making it a good candidate molecule in the treatment of cancer. However, difficulties in producing the molecule, and its short in vivo half-life, limit its use.
ALT-803 is a novel IL-15 superagonist complex, or molecule that can take on the role of IL-15. It consists of a mutant form of IL-15 (IL-15N72D) bound to an altered form of the IL-15 receptor. The drug works by triggering and enhancing the anti-tumor capacity of NK and T-cells.
ALT-803 in clinical trial for Lymphoma
In 2011, the effectiveness of ALT-803 was tested in a preclinical study comparing the drug with a non-altered form of IL-15. The results showed that ALT-803 had better pharmacokinetic properties (the way a drug moves within the body), was active for longer in the cells and organs of the lymphatic system, and produced a faster and more durable response against cancer cells, compared to non-complexed IL-15.
Another pre-clinical study designed to test the effects of ALT-803 on NK cell responses directed against primary B-cell lymphoma and cell lines in vitro and in vivo was conducted in 2016. The results of this study revealed that ALT-803 increases NK cell anti-lymphoma responses in vitro and in vivo. Moreover, the addition of ALT-803 to anti-CD20 antibody therapy resulted in significantly reduced tumor cell burden and increased survival.
These encouraging results led to Phase1/2 clinical trial (NCT02384954) testing ALT-803 plus Rituxan (rituximab) in patients with relapsed/refractory slow-growing B-Cell NHL. This trial is currently recruiting participants.
Alt-803 also will be examined as an experimental combination vaccine in Phase 1/2 (NCT03169790) and Phase 1 (NCT02890758) studies in combination with donor NK cell therapy. These trials are not yet open for participant recruitment.
A Phase1/2 clinical (NCT01885897) trial is currently recruiting patients to evaluate the effectiveness of ALT-803 as monotherapy in patients whose cancer has returned more than 60 days after allogeneic transplant as a treatment for blood cancer.
The U.S. Food and Drug Administration (FDA) recently granted fast track status to ALT-803 in combination with the bacillus Calmette-Guérin (BCG) vaccine for the treatment of patients with early bladder cancer.
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