Spotlight on pembrolizumab in the treatment of advanced melanoma

Figures & data

Figure 1 T-cell activation begins with antigen binding to the TCR complex in conjunction with other costimulatory signals.

Notes: This process can be downregulated at different points. CTLA-4 binding to B7 will block the initial priming of the T-cell (signal 1) leading to a suppression of T-cell activation. PD-1 regulates immunity at several downstream stages of the immune response. PD-1 binding by tumor-elaborated PD-L1 (or PD-L2) in peripheral tissues also leads to a suppression of T-cell activation (signal 2). The suppression of T-cell activation is a key step in allowing tumor to evade natural host tumor surveillance and defense.
Abbreviations: TCR, T-cell receptor; CTLA-4, cytotoxic T-lymphocyte-associated antigen; PD-1, programmed cell death-1; PD-L1, programmed death-ligand 1; APC, antigen presenting cell; MHC, major histocompatibility complex.

Table 1 Targeted therapies in development for modulation of PD-1 and PD-L1 functions in tumor immune surveillance

Antibody	Target
Pembrolizumab*	PD-1
Nivolumab*	PD-1
Pidilizumab	PD-1
CT-011	PD-1
AMP-224	PD-1
MDX-1105	PD-L1
MPDL3280A#	PD-L1
MEDI4736#	PD-L1
MSB0010718C	PD-L1

Notes:

* FDA approved for use in advanced melanomas.

# Clinical development indications include advanced melanomas.

Abbreviations: PD-1, programmed cell death 1; PD-L1, programmed death-ligand 1; FDA, US Food and Drug Administration.