Probody therapies are antibodies designed to bind with high selectivity to tumor cells and not to healthy tissue, so as to minimizing damage and toxicity to the body while retaining anti-tumor activity.
How CX-072 works
As a recombinant antibody, CX-072 consists of a monoclonal antibody directed against a protein called programmed cell death 1 ligand 1 (PD-L1). The PD-L1 protein is commonly overexpressed on tumor cells or cells in the tumor microenvironment.
In order to make sure that the treatment is only directed against diseased cells or tissue, the monoclonal antibody part of CX-072 is linked to a masking peptide.
When CX-072 reaches tumor cells, its masked peptide is cleaved by tumor-associated proteases (proteins that break down other proteins) and unmasked. This is thought to allow the monoclonal antibody portion of CX-072 to link to PD-L1 and prevent it from binding to T-cells — allowing those cells to activate and fight cancer.
This is because when PD-L1 binds to its receptor on T-cells, it works to suppresses those immune cells and so allow cancer cells to evade immune system checkpoints designed to protect the body against disease. By inhibiting this binding, CX-072 enhances the T-cell-mediated anti-tumor response of the immune system and leaves cancer cells less able to evade that response.
At the same time, the peptide masking of CX-072 minimizes its binding to PD-L1 in healthy tissues, potentially lessening damage to these tissues (in an autoimmune reaction) while retaining anti-tumor activity.
CX-072 in clinical trials
CX-072 is now being evaluated in an open-label and dose-escalating Phase 1/2 clinical trial (NCT03013491). The study will investigate the treatment’s safety, tolerability, pharmacokinetics (how the body affects a drug), and pharmacodynamics (how a drug affects the body), as well as its antitumor activity, in about 150 patients with metastatic or locally advanced solid tumors or lymphomas.
The study, part of CytomX’s PROCLAIM (Probody Clinical Assessment in Man) development program, is recruiting patients at more than 30 sites throughout the U.S., the U.K., Spain and Poland. It is expected to conclude in 2021.
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