TECENTRIQ (atezolizumab)

The first approved anti-PD-L1 cancer immunotherapy

Introducing the proposed mechanism of action for TECENTRIQ (atezolizumab). The first approved anti PD-L1 cancer immunotherapy. Cancer immunotherapies are designed to work with the immune system to combat cancer. The cancer immunity cycle characterizes how a person’s own immune system can help protect the body against cancer. Through a series of complex interactions, the immune system can detect tumours and activate cytotoxic t-cells to infiltrate the tumour microenvironment and attack tumour cells. When functioning optimally the cancer immunity cycle is self-sustaining, however in patients with cancer this immunity cycle can be disrupted allowing for unchecked tumour growth. Among other factors this disruption can be caused by PD-L1, instead of a negative immune regulator that can be expressed in the tumour microenvironment. Cytotoxic T cells that enter the tumour microenvironment may be deactivated by PD-L1 on tumour cells and tumour infiltrating immune cells. When PD-L1 binds to its receptors PD-1 or B7.1 on T cells, the T cells may be rendered inactive. As a result, anti-tumour immune activity may be suppressed in the tumour microenvironment causing disruption in the cancer immunity cycle. TECENTRIQ is the first approved anti PD-L1 cancer immunotherapy. TECENTRIQ targets PD-L1 in the tumour microenvironment. A key site of T cell deactivation. The proposed mechanism of action of TECENTRIQ has three distinct features. The first feature direct, TECENTRIQ is designed to bind directly to PD-L1 on tumour cells and tumour infiltrating immune cells in the tumour microenvironment. The second feature, complete. TECENTRIQ provides a dual blockade by preventing PD-L1 from binding to both the PD-1 and B7.1 receptors. Blocking interaction with PD-1 can reinvigorate suppressed T cells to kill cancer cells. Blocking interaction with B7.1 can enhance T cell priming and activation in the lymph node.

The third feature, selective. In normal tissues TECENTRIQ may help minimize autoimmune reactions. TECENTRIQ spares interactions between PD-1 and PD-L2 potentially preserving immune homeostasis in normal tissue. In clinical trials blocking PD-L1 from binding to its receptors resulted in tumour shrinkage. TECENTRIQ provides direct and complete blockade of PD-L1 interactions while selectively sparing PD-L2 interactions. This can restore antitumor T cell activity and enhanced T cell priming within the cancer immunity cycle.

For more information about TECENTRIQ the first approved anti PD-L1 cancer immunotherapy. Please contact your Roche representative.