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A Photoactive Supramolecular Complex Targeting PD-L1 Reveals a Weak Correlation between Photoactivation Efficiency
Pietro Delcanale1, Manuela Maria Alampi1, Andrea Mussini1
1Department of Mathematical, Physical and Computer Sciences, University of Parma, 43124 Parma, Italy.
Abstract:
Photo-immunotherapy uses antibodies conjugated to photosensitizers to produce nanostructured constructs endowed with targeting properties and photo-inactivation capabilities towards tumor cells. The superficial receptor density on cancer cells is considered a determining factor for the efficacy of the photodynamic treatment. In this work, we propose the use of a photoactive conjugate that consists of the clinical grade PD-L1-binding monoclonal antibody Atezolizumab, covalently linked to either the well-known photosensitizer eosin or the fluorescent probe Alexa647. Using single-molecule localization microscopy (direct stochastic optical reconstruction microscopy, dSTORM), and an anti-PD-L1 monoclonal antibody labelled with Alexa647, we quantified the density of PD-L1 receptors exposed on the cell surface in two human non-small-cell lung cancer lines (H322 and A549) expressing PD-L1 to a different level. We then investigated if this value correlates with the effectiveness of the photodynamic treatment. The photodynamic treatment of H322 and A549 with the photo-immunoconjugate demonstrated its potential for PDT treatments, but the efficacy did not correlate with the PD-L1 expression levels. Our results provide additional evidence that receptor density does not determine a priori the level of photo-induced cell death.
Insights
Photo-immunotherapy shows promise for cancer treatment, but PD-L1 receptor density on cancer cells does not predict treatment effectiveness. Further research is needed to understand factors influencing photodynamic therapy outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Bioconjugation
Background:
- Photo-immunotherapy combines antibodies and photosensitizers for targeted cancer cell inactivation.
- Superficial receptor density is often assumed to be critical for photodynamic therapy (PDT) efficacy.
Purpose of the Study:
- To investigate the correlation between PD-L1 receptor density and the effectiveness of photo-immunotherapy.
- To evaluate a novel photoactive conjugate using Atezolizumab linked to photosensitizers.
Main Methods:
- Developed a photoactive conjugate with Atezolizumab and eosin or Alexa647.
- Quantified PD-L1 receptor density on non-small-cell lung cancer cells (H322, A549) using dSTORM microscopy.
- Assessed the efficacy of photodynamic treatment with the developed conjugate.
Main Results:
- The photo-immunoconjugate demonstrated potential for PDT in H322 and A549 cell lines.
- Treatment efficacy did not correlate with the measured PD-L1 expression levels.
- Receptor density was not a determining factor for the level of photo-induced cell death.
Conclusions:
- PD-L1 receptor density does not solely determine photo-immunotherapy efficacy.
- The developed photo-immunoconjugate shows potential for PDT, but efficacy determinants require further investigation.
- This study challenges the assumption that superficial receptor density is the primary predictor of photodynamic treatment success.
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