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Near Infrared Photoimmunotherapy for Mouse Models of Pleural Dissemination
Published on: February 9, 2021
Near infrared photoimmunotherapy of B-cell lymphoma
Tadanobu Nagaya1, Yuko Nakamura1, Kazuhide Sato1
1Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, United States.
Abstract:
Near infrared photoimmunotherapy (NIR-PIT) is a new, highly-selective cancer theranostics that employs an antibody-photo absorber conjugate (APC). NIR-PIT has successfully treated preclinical tumor models with APCs and is now in the first-in-human phase 1 clinical trial for head and neck cancer patients against EGFR. CD20 is highly expressed in many B-cell lymphomas and is emerging as a molecular target for this disease. Here, we describe the use of the anti-CD20 monoclonal antibody (mAb), rituximab-IR700 APC for NIR-PIT of B-cell lymphoma in two CD20-expressing lymphoma mouse models. CD20 expressing B-cell lymphoma cell lines (Daudi and Ramos) were used in this study. Rituximab-IR700, rituximab conjugated with IRDye700DX, showed specific binding, and cell-specific killing only after exposure of NIR light to both cells in vitro. To evaluate effects of NIR-PIT in vivo, tumor-bearing mice were separated into 4 groups: (1) control; (2) APC i.v. only; (3) NIR light exposure only; (4) APC and NIR light (NIR-PIT). These were performed every week for up to 3 weeks. Rituximab-IR700 showed high tumor accumulation and high target-to-background ratio in vivo. Tumor growth was significantly inhibited by NIR-PIT in comparison with the other groups (p < 0.001 for both tumors), and survival was significantly prolonged in both tumors (p < 0.001 for Daudi tumors and p < 0.0001 for Ramos tumors vs other groups). More than half of tumors were cured with this single regimen of NIR-PIT. In conclusion, anti-CD20 rituximab-IR700 works as a highly effective APC for NIR-PIT against B-cell lymphoma.
Insights
Near infrared photoimmunotherapy (NIR-PIT) using rituximab-IR700 effectively targets CD20-expressing B-cell lymphomas. This antibody-photo absorber conjugate (APC) demonstrated significant tumor inhibition and prolonged survival in preclinical models.
Area of Science:
- Oncology
- Immunotherapy
- Photodynamic Therapy
Background:
- Near infrared photoimmunotherapy (NIR-PIT) is a selective cancer treatment using antibody-photo absorber conjugates (APCs).
- CD20 is a key molecular target for B-cell lymphomas, making it a promising target for novel therapies.
Purpose of the Study:
- To evaluate the efficacy of rituximab-IR700, an anti-CD20 antibody-photo absorber conjugate (APC), for NIR-PIT in preclinical models of B-cell lymphoma.
- To assess the in vitro and in vivo performance of rituximab-IR700 for targeted cancer therapy.
Main Methods:
- Developed rituximab-IR700, conjugating the anti-CD20 antibody rituximab with the photoabsorber IRDye700DX.
- Tested rituximab-IR700 in CD20-expressing B-cell lymphoma cell lines (Daudi and Ramos) in vitro and in tumor-bearing mouse models in vivo.
- Administered rituximab-IR700 followed by NIR light exposure weekly for up to 3 weeks, comparing outcomes to control groups.
Main Results:
- Rituximab-IR700 demonstrated specific binding and cell-killing activity in vitro upon NIR light exposure.
- In vivo studies showed high tumor accumulation and target-to-background ratios for rituximab-IR700.
- NIR-PIT with rituximab-IR700 significantly inhibited tumor growth (p < 0.001) and prolonged survival (p < 0.001 for Daudi, p < 0.0001 for Ramos) in both lymphoma models.
- Over 50% of tumors were cured with a single NIR-PIT regimen.
Conclusions:
- Anti-CD20 rituximab-IR700 is a highly effective antibody-photo absorber conjugate (APC) for NIR-PIT against B-cell lymphoma.
- NIR-PIT using rituximab-IR700 shows significant therapeutic potential for treating CD20-positive lymphomas.
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