Merck
  • Phototherapy with Cancer-Specific Nanoporphyrin Potentiates Immunotherapy in Bladder Cancer.

Phototherapy with Cancer-Specific Nanoporphyrin Potentiates Immunotherapy in Bladder Cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research (2022-08-04)
Zheng Zhu, Ai-Hong Ma, Hongyong Zhang, Tzu-Yin Lin, Xiangdong Xue, Hizra Farrukh, Shaoming Zhu, Wei Shi, Ruan Yuan, Zhixiu Cao, Veera Chandra Sekhar Reddy Chittepu, Rao Prabhala, Yuanpei Li, Kit S Lam, Chong-Xian Pan
摘要

Immune checkpoint inhibitors (ICI) in general have shown poor efficacy in bladder cancer. The purpose of this project was to determine whether photodynamic therapy (PDT) with bladder cancer-specific porphyrin-based PLZ4-nanoparticles (PNP) potentiated ICI. SV40 T/Ras double-transgenic mice bearing spontaneous bladder cancer and C57BL/6 mice carrying syngeneic bladder cancer models were used to determine the efficacy and conduct molecular correlative studies. PDT with PNP generated reactive oxygen species, and induced protein carbonylation and dendritic cell maturation. In SV40 T/Ras double-transgenic mice carrying spontaneous bladder cancer, the median survival was 33.7 days in the control, compared with 44.8 (P = 0.0123), 52.6 (P = 0.0054), and over 75 (P = 0.0001) days in the anti-programmed cell death-1 antibody (anti-PD-1), PNP PDT, and combination groups, respectively. At Day 75 when all mice in other groups died, only 1 in 7 mice in the combination group died. For the direct anti-tumor activity, compared with the control, the anti-PD-1, PNP PDT, and combination groups induced a 40.25% (P = 0.0003), 80.72% (P < 0.0001), and 93.03% (P < 0.0001) tumor reduction, respectively. For the abscopal anticancer immunity, the anti-PD-1, PNP PDT, and combination groups induced tumor reduction of 45.73% (P = 0.0001), 54.92% (P < 0.0001), and 75.96% (P < 0.0001), respectively. The combination treatment also diminished spontaneous and induced lung metastasis. Potential of immunotherapy by PNP PDT is multifactorial. In addition to its potential for photodynamic diagnosis and therapy, PNP PDT can synergize immunotherapy in treating locally advanced and metastatic bladder cancer. Clinical trials are warranted to determine the efficacy and toxicity of this combination.

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Sigma-Aldrich
MB49小鼠膀胱癌细胞系, MB49 mouse urothelial carcinoma cell line is widely used as an in vitro and in vivo model of bladder cancer.