2024 World Conference on Lung Cancer (WCLC) - Posters-P1.03D.08 Padeliporphin VTP Reverts NSCLC Orthotopic Tumors in Animal Models Into Highly Responsive to aPD1 Therapy

P1.03D.08 Padeliporphin VTP Reverts NSCLC Orthotopic Tumors in Animal Models Into Highly Responsive to aPD1 Therapy

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The study investigates the potential of combining Padeliporfin-based vascular targeted photodynamic therapy (VTP) with immune checkpoint inhibitors (ICIs) to improve treatment efficacy for non-small cell lung cancer (NSCLC) in animal models. Despite the promise shown by ICIs such as anti-CTLA-4 and anti-PD-1 treatments in NSCLC, outcomes have been underwhelming, necessitating strategies to enhance antitumor immunity.<br /><br />The research utilizes C57BL/6 mice with orthotopic LLC-Luc-mCherry tumors, administering a low light dose of Padeliporfin VTP complemented by multiple doses of aCTLA-4 and aPD-1. This protocol was tested against control conditions and variations of treatments. Results demonstrated that the combination of VTP with ICIs led to a significant enhancement in survival and tumor eradication compared to single-agent treatments. Specifically, the synergistic combination of VTP with both aPD1 and aCTLA4 achieved the highest cure rates.<br /><br />Tumor evaluation included bioluminescence imaging, histology, and micro-CT, showing that the VTP treatment increased the invasion of immune cells into the tumor microenvironment, triggered necrosis, and altered PD1 and PDL1 expression levels. This modulation led to heightened immune activation, notably increasing CD8 T cells and dendritic cells shortly after VTP administration, which shifted toward a more effective antitumor response.<br /><br />The study concludes that combining Padeliporfin VTP with ICIs offers a promising therapeutic approach and will be further evaluated in a Phase 1 clinical trial for peripheral lung cancer. Results suggest that the VTP method may effectively convert NSCLC tumors into a form that is more receptive to checkpoint inhibitor therapies, potentially improving overall patient outcomes.

Asset Subtitle

David Kain

Meta Tag

Speaker David Kain

Topic Tumor Biology – Translational Biology

Keywords

Padeliporfin

vascular targeted photodynamic therapy

immune checkpoint inhibitors

non-small cell lung cancer

NSCLC

anti-CTLA-4

anti-PD-1

tumor microenvironment

CD8 T cells

Phase 1 clinical trial