In a preclinical study presented at the 2017 AACR Annual Meeting, BION-1301, an anti-human APRIL blocking antibody, inhibited the survival of multiple myeloma (MM) cells.
Patients with MM, chronic lymphocytic leukemia, and colorectal carcinoma are known to have higher APRIL (a proliferation-inducing ligand or tumor necrosis factor super family member 13) serum levels, which is produced by cells in the bone marrow niche. APRIL binds to receptors of B-cell maturation antigens and negatively affects survival and induces resistance to certain anti-cancer drugs.
“To our knowledge, BION-1301 is a first-in-class humanized APRIL antagonist demonstrated to inhibit survival of MM cells, drug resistance, and an immune suppressive phenotype preclinical,” according to John Dulos, PhD, of Aduro Biotech Europe in Oss, the Netherlands, and co-authors.
To develop BION-1301, Dr. Dulos and colleagues humanized a novel mouse anti-human APRIL antibody, and engineered the antibody to enhance its stability. BION-1301 suppressed APRIL-induced B-cell IgA and IgG class switching in vitro in a dose-dependent fashion.
Biophysical and functional experiments indicated that BION-1301 recapitulated all characteristics of the murine model. In vivo, BION-1301 suppressed T cell-independent B-cell responses to the antigen NP-Ficoll. In addition, a humanized SCID model confirmed APRIL blockade, supporting the activity of BION-1301 in vivo. “[This] potentially indicates that BION-1301 is active in targeting MM cells in a tumor-protective bone marrow microenvironment,” Dr. Dulos and co-authors noted.
“These data suggest a rationale to develop BION-1301 as a single agent and in combination with lenalidomide, bortezomib, or possibly checkpoint inhibitors, such as anti-PD-1,” Dr. Dulos and co-authors concluded.
The study was sponsored by the agent’s manufacturer. The authors noted that BION-1301 is expected to begin phase I trials this year.
Dulos J, Driessen L, Snippert M, et al. Development of a first in class APRIL fully blocking antibody BION-1301 for the treatment of multiple myeloma. 2645/4. Presented at the 2017 AACR Annual Meeting, April 3, 2017; Washington, DC.