Combination Strategy

Building on the foundation of PD-L1 checkpoint inhibition

PD-L1 inhibition is a clinically validated approach to invigorating existing immunity. However, tumours employ multiple mechanisms to evade the immune response, which disrupts the cancer immunity cycle. By using our understanding of immune phenotypes, our rational combination approach can address these mechanisms of immune escape to generate the essential T-cell activities required for each patient.1

 

 
 
 
 
 
 
Examples of combination strategies by immune phenotype*
  • Chemotherapy/targeted therapy:
    • promotes tumour cell death, resulting in the release of tumour antigens that can initiate T-cell priming and activation3
  • PD-L1 inhibition:
    • blocks immunosuppressive signalling in the tumour microenvironment to invigorate T-cell–mediated tumour killing1
  • VEGF inhibition:
    • helps increase T-cell infiltration into the tumour microenvironment1
  • PD-L1 inhibition:
    • blocks immunosuppressive signalling in the tumour microenvironment to invigorate T-cell–mediated tumour killing1
  • Additional immunomodulatory targets + PD-L1 inhibition:
 
*Mapping of pathways to phenotypes based on current lead hypotheses. Does not preclude activity in other phenotypes
 
References 
  1. Kim JM, Chen DS. Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure). Ann Oncol. 2016;27:1492-1504. PMID: 27207108
  2. Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541:321-330. PMID: 28102259
  3. Swart M, Verbrugge I, Beltman JB. Combination approaches with immune-checkpoint blockade in cancer therapy. Front Oncol. 2016;6. doi:10.3389/fonc.2016.00233. PMID: 27847783

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