Atezolizumab

Atezolizumab (also known as MPDL3280A, commercial name Tecentriq) is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein Programmed cell death-ligand 1. It is currently in clinical trials as an immunotherapy for several types of solid tumors. It is under investigation by Genentech/Roche.

In May 2016 it was approved by the FDA for bladder cancer treatment.

In April, 2016 Roche announced that atezolizumab had been granted fast track status for lung cancer by the FDA.

Medical uses

In May 2016 FDA granted accelerated approval to atezolizumab for locally advanced or metastatic urothelial carcinoma treatment after failure of chemo or radio therapy.

Clinical trials

It is currently on clinical trials for colorectal cancer, melanoma, breast cancer, non-small-cell lung carcinoma, bladder cancer, renal cell carcinoma.

Promising results have been observed for melanoma and non-small-cell lung cancer, and bladder cancer.

A phase 1 trial reported a 19% objective response rate in metastatic triple-negative breast cancer.

Mechanism of action

Atezolizumab blocks the interaction of PD-L1 with PD-1 and B7.1. PD-L1 can be highly expressed on certain tumors, which is thought to lead to reduced activation of immune cells (cytotoxic T-cells in particular) that might otherwise recognize and attack the cancer. Inhibition of PD-L1 by atezolizumab can remove this inhibitor effect and thereby engender an anti-tumor response. It is one of several ways to block inhibitory signals related to T-cell activation, a more general strategy known as "immune checkpoint inhibition."

For some cancers (notably bladder) the probability of benefit is related to PD-L1 expression, but most cancers with PD-L1 expression still do not respond, and many (about 15%) without PD-L1 expression do respond.