Abstract 3831: Development of near-infrared photoimmunotherapy targeting GD2-positive neuroblastoma

Abstract

Background: Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system. Despite the recent advances in the treatment of NB, patients with high-risk NB still have poor prognosis. Immunotherapy using anti-GD2 monoclonal antibody (mAb), which binds to disialoganglioside GD2 on the surface of NB cells, has recently become a standard treatment for high-risk NB. However, the therapeutic efficacy of anti-GD2 mAb is insufficient in many clinical trials. Therefore, the enhancement of therapeutic potential of anti-GD2 mAb is needed to improve the clinical outcome of patients with high-risk NB. Near-infrared photoimmunotherapy (NIR-PIT) is a promising antitumor strategy to enhance the therapeutic potential of immunotherapy using an antibody-photoabsorber conjugate (APC). In this study, we investigated the therapeutic efficacy of anti-GD2-based NIR-PIT using anti-GD2 mAb conjugated to the photoabsorber IR700 (anti-GD2-IR700) in human NB cells. Methods: We used 3 human NB cell lines, including IMR-32, CHP-134 and SK-N-SH. The expression of GD2 on the cell surface of NB cells was analyzed by flow cytometric analysis. Anti-GD2-IR700 was synthesized by incubating anti-GD2 mAb and IR700. The mixture was purified with a Sephadex G50 column. The antitumor effect of anti-GD2-IR700 was evaluated using XTT assay. NB cells were incubated with anti-GD2-IR700, anti-GD2 mAb or PBS and NIR light was irradiated at 2.0J/cm2. Results: IMR-32 and CHP-134 cells, but not SK-N-SH cells, expressed GD2 protein on the cell surface. In GD2-positive IMR-32 and CHP-134 cells, administration of anti-GD2-IR700 significantly suppressed the cell viability compared to anti-GD2 mAb or PBS when combined with NIR light irradiation. In contrast, in GD2-negative SK-N-SH cells, anti-GD2-IR700 showed no significant inhibition of cell viability in combination with NIR light irradiation. Conclusion: These results suggest that NIR-PIT using an anti-GD2-IR700 is a promising antitumor strategy to promote the therapeutic efficacy of anti-GD2 immunotherapy for high-risk NB. Citation Format: Hiroshi Nouso, Hiroshi Tazawa, Terutaka Tanimoto, Morimichi Tani, Takanori Oyama, Hiroaki Sato, Kazuhiro Noma, Shunsuke Kagawa, Hisataka Kobayashi, Takuo Noda, Toshiyoshi Fujiwara. Development of near-infrared photoimmunotherapy targeting GD2-positive neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3831.

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“…Nouso et al showed that the administration of anti-GD2-IRDye700DX followed by NIR-PIT significantly suppressed cell viability compared to an anti-GD2 monoclonal antibody. Thus, their results showed NIR-PIT as a promising anti-tumour strategy to enhance the therapeutic efficacy of anti-GD2 immunotherapy for high-risk NB ( 91 ). Maruoka et al ( 92 ) hypothesised that the administration of IL-15 with cancer cell-targeted NIR-PIT could increase anti-tumour host immunity.…”

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“…In particular, NIR-PIT causes direct (Figure 3-panel B) and indirect (Figure 3-panel C) cell killing because the cell membrane rupture releases tumourspecific antigens into the TME and promotes dendritic cell (DC) maturation, resulting in the presentation of cancer-specific antigens on DCs to naive T cells. At the American Association for Cancer Research meeting in 2018, Hiroshi Nouso et al [49] presented the use of NIR-PIT with an anti-GD2-IR700 as a promising anti-tumour strategy to enhance the therapeutic efficacy of anti-GD2 immunotherapy for high-risk NB. They evaluated the anti-tumour effect of anti-GD2-IR700 on three human NB cell lines, showing that the administration of anti-GD2-IR700 significantly suppressed the cell viability compared to anti-GD2 mAb when combined with NIR light irradiation.…”