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 characterises 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-1 or PD-L1, 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:
DIRECT: TECENTRIQ is designed to bind directly to PD-L1 on tumour cells and tumour infiltrating immune cells in the tumour microenvironment.
COMPLETE: TECENTRIQ provides a dual blockade by preventing PD-L1 from binding to both the PD-1 and B7.1 receptor. 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.
SELECTIVE: In normal tissues TECENTRIQ may help minimise 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.
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