Cancer Immunotherapy

immunotherapy

not chemotherapy as does not use small molecule chemical drugs

uses ‘biologics’ like monoclonal antibodies, referred to as checkpoint inhibitors

Ipilimumab

2011

first immune checkpoint inhibitor approved

Pembrolizimab and Nivolumab

2014

2 new checkpoint inhibitors approved

(now >150 in clinical trials)

Nivolumab binds PD1

how do cancer cells achieve immunoevasion

are effective at suppressing T cells even though TcRs are able to recognise abnormal antigens on cancer cells

present surface proteins which can interact with other T cell surface proteins that tell it to ignore the cancer cell (immune checkpoint)

PD-L1 is overexpressed on 40-80% of melanoma cancer cells and binds PD1 and B7.1 on T cells to switch them off

immunotherapy mode of action

block interactions between PDL1 with PD1 and B7.1 to switch the T cell back on and trigger killing of cancer cells

use a mAb raised by bind PD1 and/or PDL1 (checkpoint inhibitors)

disadvantage of checkpoint inhibitors

far more expensive to produce than small drug molecules