Immunotherapy: a New Bispecific Antibody to Treat B-cell Lymphoma and Leukemia
Samples from the CeVi collection of the CALYM Carnot Institute were used in the preclinical studies published by Novimmune SA on a new bispecific antibody targeting CD19 and CD47*.
The most widely used treatment for B-cell lymphomas is CHOP chemotherapy combined with anti-CD20 rituximab antibody. However, 30-60% of indolent patients are resistant to rituximab at baseline and up to 50% of relapse after treatment and become refractory.
Researchers at Novimmune SA have developed a new bispecific antibody, NI-1701, targeting CD19 and CD47. CD19 is a transmembrane glycoprotein widely expressed in B cell malignancies including those positive for CD20 or not. CD47 is a ubiquitously expressed protein that mediates a “don’t eat me” signal by interacting with SIRP1a regulatory protein expressed by macrophages and thereby blocking their phagocytosis function. CD47 is overexpressed by cancer cells, which can escape sentinels of the immune system. The goal of NI-1701 is to block CD47 interaction specifically on tumor B cells presenting CD19 antigen and thus limit hematotoxic side effects.
The researchers showed that their antibody did not bind to erythrocytes or T cells and weakly to platelets and was well tolerated in non-human primates.
They tested, in collaboration with the “Microenvironment Cell differentiation, iMmunology And Cancer” CALYM team of Rennes, its anti-tumor activity in vitro on cancer cell lines and primary cells, in part from the CeVi collection, of patients with leukemia (chronic lymphocytic and acute lymphoblastic leukemia) and B-cell lymphoma (marginal zone lymphoma, Waldenström macroglobulinemia, mantle cell, follicular, diffuse large B cell lymphoma). They showed that NI-1701 effectively killed cancer cells by phagocytosis of macrophages.
Then they tested NI-1701 in vivo on mouse models – Burkitt’s lymphoma Raji cell line and primary cells of patients with acute lymphoblastic leukemia – and showed that it had a significant anti-tumor activity and increase in the median survival time of animals. Its activity was superior to rituximab in reducing tumor growth. Finally, the combination of both antibodies was even more effective and multiplied by 2.45 the survival time of mice.
In conclusion, the new bispecific antibody NI-1701, developed by Novimmune SA, paves the way to a relatively safe alternative treatment for patients resistant and/or refractory to anti-CD20 therapy. Clinical studies will still have to validate this new therapeutic approach.
* Preclinical development of a bispecific antibody that safely and effectively targets CD19 and CD47 for the treatment of B cell lymphoma and leukemia. Buatois et al., Mol Cancer Ther. 2018 May 9.
