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Near-infrared photoimmunotherapy for osteosarcoma targeting epidermal growth factor receptor

Motofumi Suzuki1, Hisataka Kobayashi2, Hirofumi Hanaoka1

  • 1Division of Fundamental Technology Development, Near InfraRed Photo-ImmunoTherapy Research Institute at Kansai Medical University, 2-5-1, Shin-Machi, Hirakata, Osaka, 573-1010, Japan.

Translational Oncology
|October 2, 2024
PubMed

Insights

Near-infrared photoimmunotherapy (NIR-PIT) targeting epidermal growth factor receptor (EGFR) shows promise for treating osteosarcoma. This novel therapy induces immunogenic cell death and suppresses tumor growth, offering potential for primary and metastatic bone cancers.

Area of Science:

  • Oncology
  • Biomedical Engineering
  • Cancer Therapy

Background:

  • Osteosarcoma is a common bone tumor with high metastatic potential, and current treatments have limited efficacy for advanced disease.
  • Systemic chemotherapy has plateaued in improving survival rates for osteosarcoma, particularly for metastatic cases.
  • Near-infrared photoimmunotherapy (NIR-PIT) is an emerging cancer treatment that leverages targeted cell death induction and stimulates systemic anti-tumor immunity.

Purpose of the Study:

  • To investigate the efficacy of NIR-PIT targeting epidermal growth factor receptor (EGFR) in osteosarcoma.
  • To evaluate the impact of EGFR expression levels on NIR-PIT's cytotoxic effects in osteosarcoma cell lines.
  • To determine if NIR-PIT can induce immunogenic cell death (ICD) and suppress tumor growth in osteosarcoma models.

Main Methods:

  • Evaluation of NIR-PIT's cytotoxic effects on osteosarcoma cell lines (MG63 and Saos-2) with varying EGFR expression.
  • Microscopic observation of characteristic cell morphology changes post-NIR-PIT, including swelling and bleb formation.
  • Measurement of ICD markers (lactate dehydrogenase and ATP) release after NIR-PIT treatment.
  • Assessment of NIR-PIT's anti-tumor efficacy in a mouse model bearing osteosarcoma tumors.

Main Results:

  • NIR-PIT-induced cell death in osteosarcoma was dependent on the level of EGFR expression.
  • Characteristic morphological changes associated with NIR-PIT-induced necrosis were observed.
  • Significant release of ICD markers, lactate dehydrogenase and ATP, confirmed immunogenic cell death induction.
  • NIR-PIT treatment significantly suppressed tumor growth in vivo in tumor-bearing mice.

Conclusions:

  • Targeting EGFR with NIR-PIT demonstrates therapeutic potential in osteosarcoma.
  • NIR-PIT effectively induces immunogenic cell death in osteosarcoma cells.
  • This approach presents a promising novel therapeutic strategy for both primary and metastatic osteosarcoma.
Keywords:
EGFRImmunogenic cell deathNear-infrared photoimmunotherapyOsteosarcomaTumor treatment

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