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About IMFINZI

The role of PD-L11

  • Expression of PD-L1 is an adaptive immune response that helps tumours evade detection and elimination by the immune system
  • PD-L1 can be expressed on both tumour cells and tumour-associated immune cells in the tumour microenvironment
    - PD-L1 expression can be induced by inflammatory signals (eg, IFNγ)
  • By binding to its receptors, PD-L1 reduces cytotoxic T cell activity, proliferation, and cytokine production

The PD-L1 pathway and tumour progression

In pre-clinical models, increased PD-L1 expression following radiation has been observed2,3
  • Radiation induces tumour cell death, releasing a diverse array of tumour antigens4-6
  • As a result, PD-L1 is upregulated, inhibiting T cell activity and promoting tumour regrowth2,3

IMFINZI mechanism of action

In pre-clinical studies, IMFINZI enhances immune response1

  • IMFINZI is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that blocks the interaction of PD-L1 with PD-1 and CD80
  • Selective blockade of PD-L1/PD-1 and PD-L1/CD80 interactions enhances anti-tumour immune responses
  • In pre-clinical studies, PD-L1 blockade led to increased T cell activation

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CD80: cluster of differentiation 80; IFNγ: interferon gamma; PD-1: programmed death-1; PD-L1: programmed death ligand-1

References: 1. Draft IMFINZI Summary of Product Characteristics. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018. 2. Dovedi SJ, Adlard AL, Lipowska-Bhalla G, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 2014;74(19):5458-5468. 3. Deng L, Liang H, Burnette B, et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 2014;124(2):687-695. 4. Lugade AA, Moran JP, Gerber SA, Rose RC, Frelinger JG, Lord EM. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol. 2005;174(12):7516-7523. 5. Reits EA, Hodge JW, Herberts CA, et al. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med. 2006;203(5):1259-1271. 6. Chakraborty M, Abrams SI, Coleman CN, Camphausen K, Schlom J, Hodge JW. External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing. Cancer Res. 2004;64(12):4328-4337.