Obinutuzumab in kidney transplantation: Past, present, and future

Table 1 Main anti-B-cell agents with potential use in kidney transplantation

Drug	Approval	Target	Structure	CDC	ADCC	ADCP	DCD	Notes/unique properties
Rituximab	1997 (FDA/EMA)	Type 1 anti-CD20	Chimeric IgG1κ (mouse-human)	+++	++	++	±	First approved anti-CD20 monoclonal antibody; complement-dependent; widely used
Obinutuzumab	2013 (FDA); 2014 (EMA)	Type 2 anti-CD20	Glycoengineered humanized IgG1	+	+++	++	+++	Enhanced ADCC, ADCP and DCD; low CDC; resistant to complement inhibition, high-dose IgG, and trogocytosis
Ofatumumab	2009 (FDA)	Type 1 anti-CD20	Fully human IgG1κ	++++	+	+	-	Strong CDC; high affinity for CD20 membrane-proximal epitope
Ocrelizumab	2017 (FDA/EMA)	Type 1 anti-CD20	Humanized IgG1	++	++	+	±	Reduced immunogenicity vs RTX
Ublituximab	2022 (FDA)	Type 1 anti-CD20	Glycoengineered chimeric IgG1	++	+++	++	±	Enhanced FcγRIIIA binding; increased ADCC
Inebilizumab	2020 (FDA)	Anti-CD19	Humanized IgG1	++	++	++	±	CD19-depleting agent; long-lived plasma cells modulation
Belimumab	2011 (FDA/EMA)	BLyS-inhibitor	Human IgG1λ	-	-	-	-	Inhibits B-cell survival factor B-cell activating factor
Daratumumab	2015 (FDA); 2016 (EMA)	Anti-CD38	Human IgG1κ	+++	+++	+++	++	Targets CD38 on plasma cells and activated B cells/T cells; depletes donor-specific anti-HLA antibodies-producing clones; synergizes with anti-CD20

+ to ++++: Reflects relative strength of activity; ±: Variable or minimal activity; –: Absent activity; ADCC: Antibody-dependent cell-mediated cytotoxicity; ADCP, antibody-dependent cell phagocytosis; CDC: Complement-dependent cytotoxicity; DCD: Direct cell death; EMA: European Medicines Agency; FcγR: Fragment crystallizable receptor; FDA: Food and Drug Administration; IgG: Immunoglobulin G; RTX: Rituximab.