Atezolizumab

Atezolizumab
Monoclonal antibody
Type Whole antibody
Source Humanized
Legal status
Legal status
  • Investigational
Identifiers
CAS Number 1380723-44-3
ChemSpider none
UNII 52CMI0WC3Y

Atezolizumab (also known as MPDL3280A) is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death ligand 1 (PD-L1). It is currently in clinical trials as an immunotherapy for several types of solid tumors.[1] It is under investigation by Genentech/Roche.

Medical uses

None approved.

In April, 2016 Roche announced that atezolizumab had been granted fast track status by the FDA.[2]

Clinical trials

It is currently on clinical trials for melanoma, breast cancer, non-small-cell lung carcinoma, bladder cancer, renal cell carcinoma.[3]

Promising results have been observed for melanoma and non-small-cell lung cancer, and bladder cancer.[1]

A phase 1 trial reported a 19% objective response rate in metastatic triple-negative breast cancer.[4]

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.

References

  1. 1 2 "Genentech Presents Positive Results of Atezolizumab in Advanced Bladder Cancer". Oct 2, 2015.
  2. ↑ Shields, Michael (11 Apr 2016). "Roche says FDA fast tracks atezolizumab in specific type of lung cancer". Reuters. Retrieved 11 Apr 2016.
  3. ↑ All NCT trials including MPDL3280A
  4. ↑ MPDL3280A Shows Activity in Triple-Negative Breast Cancer. March 2016


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