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Near infrared photoimmunotherapy of B-cell lymphoma.

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.

journal_name

Mol Oncol

journal_title

Molecular oncology

authors

Nagaya T,Nakamura Y,Sato K,Harada T,Choyke PL,Kobayashi H

doi

10.1016/j.molonc.2016.07.010

subject

Has Abstract

pub_date

2016-11-01 00:00:00

pages

1404-1414

issue

9

eissn

1574-7891

issn

1878-0261

pii

S1574-7891(16)30070-9

journal_volume

10

pub_type

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