Cancer cells overexpressing CD47 receptors often evade innate immune responses as CD47 interacts with SIRPα, an inhibitory immunoreceptor expressed on phagocytes, protecting them from phagocytosis. Anti-CD47 antibodies can bind to these receptors and block this signal, enabling macrophages to target and destroy cancer cells. While promising, clinical benefits have been limited, highlighting the need for deeper understanding of their mechanisms.
A key question is whether anti-CD47 antibodies act solely by blocking CD47/SIRPα via the Fab domain or also through Fc–FcγR interactions. Osorio et al. explored this by engineering antibodies with Fc regions of varying FcγR affinities. Antibodies with higher FcγR affinity demonstrated superior antitumour activity, markedly reducing primary tumour growth and lung metastases across multiple mouse models. These findings highlight the critical role of Fc-mediated immune engagement in enhancing therapeutic efficacy.
BSI was proud to contribute our antibody sequencing services, DeepAB, to perform high-accuracy mass spectrometry-based de novo sequencing of the anti-CD47 variable regions, which were then used to engineer antibodies with modified Fc regions. Our service provided in-depth sequence coverage using multi-enzyme digests and high-resolution mass spectrometry data, analysed in our PEAKS AB software. The sequences were validated by matching the theoretical mass of bottom-up sequence assemblies to intact mass measurements. In addition, leucine/isoleucine differentiation, PTM analysis, and glycan profiling are including in this service. Taken together, our DeepAB workflow ensures highly accurate de novo sequencing and in-depth antibody characterisation.
We are honored to be part of such impactful research and proud to support innovations that advance cancer immunotherapy. If you’re interested in our antibody sequencing services or want to see how we can support your research, contact us today to learn how BSI can help accelerate your discoveries!
Read the full article here: Osorio, J. C., Smith, P., Knorr, D. A., & Ravetch, J. V. (2023). The antitumor activities of anti-CD47 antibodies require Fc-FcγR interactions. Cancer Cell, 41(12). doi:10.1016/j.ccell.2023.10.007