This week PNAS published research article that should be interesting for people following advances in cancer immunotherapy. This new study showed that in mice neither monotherapy with anti-CD47 antibody alone nor its combination with cancer-specific antibody could provide any lasting anti-cancer benefit. However, when combined in addition with anti-PDL1 checkpoint inhibitor, triple combination delivered long-lasting cancer protection.
For this study the authors generated novel high affinity anti-mouse CD47 nanobody that could enhance in vitro cancer cell [melanoma] phagocytosis by macrophages when combined with cancer-specific antibody.
However, in vivo, CD47 nanobody, A4, failed as a (1) monotherapy against melanoma challenge, (b) it couldn't enhance anti-cancer effect when combined with cancer-specific antibody (TA99), (c) it couldn't enhance anti-cancer effect of GM-CSF–producing B16F10 cells vaccine (GVAX) and (d) it slightly improved tumor protection when combined with checkpoint inhibitor PD-L1 antibody.
But, when CD47 nanobody, A4, was combined in triple combination with cancer-specific antibody (TA99) and checkpoint inhibitor PD-L1 antibody, it delivered long-lasting tumor protection in 60% of recipients against primary as well as to secondary tumor challenge indicating tumor-specific memory generation.
In summary, this study revealed that anti-CD47 antibody alone showed minimal activity when used against tumor in hosts with intact immune system (senior author of this study is involved in biotech company focusing on CD47 application). The authors suggested that earlier studies reached different results because they used immunodeficient mouse models [NOD-scid, IL2rgKO (NSG) mice] that lack intact adaptive immune system.