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Updated: Dec 30, 2025
Near Infrared Photoimmunotherapy for Mouse Models of Pleural Dissemination
Published on: February 9, 2021
Near infrared photoimmunotherapy targeting DLL3 for small cell lung cancer
Yoshitaka Isobe1, Kazuhide Sato2, Yuko Nishinaga1
1Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Background:
Small cell lung cancer (SCLC) has a poor prognosis, and its treatment options are limited. Delta-like protein 3 (DLL3) is expressed specifically in SCLC and is considered a promising therapeutic target for patients with this disease. Rovalpituzumab tesirine (Rova-T) was the first antibody-drug conjugate targeting DLL3. Although Rova-T development was unfortunately terminated, DLL3 remains an ideal target for SCLC. Near infrared photoimmunotherapy (NIR-PIT) is a new form of cancer treatment that employs an antibody-photosensitiser conjugate followed by NIR light exposure and damage target cells specifically. In this study, we demonstrate DLL3-targeted NIR-PIT to develop a novel molecularly targeted treatment for SCLC.
Methods:
The anti-DLL3 monoclonal antibody rovalpituzumab was conjugated to an IR700 photosensitiser (termed 'rova-IR700'). SCLC cells overexpressing DLL3 as well as non-DLL3-expressing controls were incubated with rova-IR700 and then exposed to NIR-light. Next, mice with SCLC xenografts were injected with rova-IR700 and irradiated with NIR-light.
Findings:
DLL3-overexpressing cells underwent immediate destruction upon NIR-light exposure, whereas the control cells remained intact. The xenograft in mice treated with rova-IR700 and NIR-light shrank markedly, whereas neither rova-IR700 injection nor NIR-light irradiation alone affected tumour size.
Interpretation:
Our data suggest that targeting of DLL3 using NIR-PIT could be a novel and promising treatment for SCLC.
Funding:
Research supported by grants from the Program for Developing Next-generation Researchers (Japan Science and Technology Agency), KAKEN (18K15923, JSPS), Medical Research Encouragement Prize of The Japan Medical Association, The Nitto Foundation, Kanae Foundation for the Promotion of Medical Science.
Insights
Targeting Delta-like protein 3 (DLL3) with near-infrared photoimmunotherapy (NIR-PIT) effectively destroyed small cell lung cancer (SCLC) cells and tumors. This DLL3-targeted NIR-PIT shows promise as a novel treatment for SCLC.
Area of Science:
- Oncology
- Immunotherapy
- Molecularly Targeted Therapy
Background:
- Small cell lung cancer (SCLC) presents a significant clinical challenge with limited therapeutic options.
- Delta-like protein 3 (DLL3) is a highly specific biomarker and therapeutic target for SCLC.
- Previous DLL3-targeted therapies, like Rovalpituzumab tesirine (Rova-T), faced development challenges, highlighting the need for alternative approaches.
Purpose of the Study:
- To investigate the efficacy of Delta-like protein 3 (DLL3)-targeted near-infrared photoimmunotherapy (NIR-PIT) as a novel treatment modality for SCLC.
- To evaluate the specific cell-killing capacity and in vivo tumor reduction potential of this targeted approach.
Main Methods:
- Conjugation of the anti-DLL3 antibody rovalpituzumab with the photosensitizer IR700 to create 'rova-IR700'.
- In vitro testing involved incubating DLL3-overexpressing SCLC cells and control cells with rova-IR700, followed by near-infrared (NIR) light exposure.
- In vivo studies utilized mice bearing SCLC xenografts, administering rova-IR700 and subsequent NIR light irradiation.
Main Results:
- NIR-light exposure led to the specific and immediate destruction of DLL3-overexpressing SCLC cells, while control cells remained unaffected.
- Mice treated with rova-IR700 and NIR-light exhibited significant shrinkage of SCLC xenografts.
- Neither rova-IR700 administration alone nor NIR-light irradiation alone demonstrated any impact on tumor size.
Conclusions:
- DLL3-targeted NIR-PIT demonstrates potent and specific anti-cancer activity against SCLC.
- This approach offers a promising new avenue for developing molecularly targeted therapies for SCLC patients.
- The findings support further investigation of NIR-PIT as a viable treatment strategy for SCLC.
