TABLE 2.

A list of the monoclonal antibodies that have been developed or are currently in development that serve as ICIs targeting PD‐1, PD‐L1 and CTLA‐4 in the treatment of HCC. The majority of them are specifically selected for their antibody class and genetic engineering through single or multiple point mutations in their Fc region in order to reduce unwanted off‐target or cytotoxic side effects. This is primarily due to a reduction (↓) or complete abrogation (↓↓↓) in the interaction between the Fc portion of the monoclonal antibody and effector cells expressing Fcγ receptors (FcγRs) which, in turn, reduces antibody‐dependant cellular cytotoxicity (ADCC), antibody‐dependant cellular phagocytosis (ADCP) and complement‐dependant cytotoxicity (CDC). Ipilimumab and Tremelimumab both target CTLA‐4 which upregulates (↑) ADCC against Treg cells, with no discernible effects on Fc/FcγR interaction (given that they are both wild‐type monoclonal antibodies) or ADCP/CDC in human models(‐).

Monoclonal antibody	Ligand target	Antibody class	Fc engineering	Fc/FcγR interaction	Mechanism of action
					ADCC	ADCP	CDC
Nivolumab	PD‐1	IgG4	S228P	↓	↓	↓	↓
Pembrolizumab	PD‐1	IgG4	S228P	↓	↓	↓	↓
Camrelizumab	PD‐1	IgG4	S228P	↓	↓	↓	↓
Tislelizumab	PD‐1	IgG4	S228P/E233P/F234V/L235A/D265A/R409K	↓↓↓	↓	↓	↓
Atezolizumab	PD‐L1	IgG1	N298A	↓↓↓	↓	↓	↓
Durvalumab	PD‐L1	IgG1	L234F/L235E/P331S	↓↓↓	↓	↓	↓
Ipilimumab	CTLA‐4	IgG1	Wild‐type	‐	↑	‐	‐
Tremelimumab	CTLA‐4	IgG2	Wild‐type	‐	↑	‐	‐