Tissue factor targeted near-infrared photoimmunotherapy: a versatile therapeutic approach for malignancies

Sep 23, 2026

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Tissue factor (TF) is a cell-surface protein involved in blood clotting and commonly expressed across many cancers, where it contributes to proliferation, metastasis, angiogenesis, and immune escape. The study develops and tests TF-targeted near-infrared photoimmunotherapy (NIR-PIT) using the TF antibody Tisotumab conjugated to IR700. TF expression was confirmed in vitro and in vivo, with light-dose-dependent cancer cell death in multiple cell lines. In xenograft models, NIR-PIT suppressed tumor growth, improved survival, and induced histological signs of cancer cell damage and death.

LanguageEnglish

CategoryHealthcare

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Pages14

Reading Time35 min

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Abstract

Introduction

Materials and methods

Cancer Immunology, Immunotherapy (2025) 74:48 [https://doi.org/10.1007/s00262-024-03903-2](https://doi.org/10.1007/s00262-024-03903-2) Tissue factor targeted near‑infrared photoimmunotherapy: a versatile therapeutic approach for malignancies Seiichiro Takao1 · Hiroshi Fukushima1 · Aki Furusawa1 · Takuya Kato1 · Shuhei Okuyama1 · Makoto Kano1 · Hiroshi Yamamoto1 · Motofumi Suzuki1 · Miyu Kano1 · Peter L. Choyke1 · Hisataka Kobayashi1 Received: 12 June 2024 / Accepted: 20 November 2024 / Published online: 3 January 2025 This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024 Abstract Tissue factor (TF) is a cell surface protein that plays a role in blood clotting but is also commonly expressed in many cancers. Recent research implicated TF in cancer proliferation, metastasis, angiogenesis, and immune escape. Therefore, TF can be considered a viable therapeutic target against cancer. Herein, we developed and tested a TF-targeted near-infrared photoimmunotherapy (NIR-PIT) as a potential treatment for several types of cancer. Tisotumab, a TF antibody, was conjugated to IR700 . The efficacy of TF-targeted NIR-PIT was investigated using multiple cancer cell lines (A431; epidermoid carcinoma, HPAF-II; pancreatic adenocarcinoma, HSC-2; oral carcinoma, HT1376-luc; bladder carcinoma, MDAMB231; breast adenocarcinoma, and SKOV3-luc; ovarian serous cystadenocarcinoma) in vitro. In vivo, the efficacy of TF-targeted NIR-PIT was evaluated in HPAF-II and A431 xenograft mouse models. Pathologic changes in these tumors after NIR-PIT were evaluated in these tumor models. All cancer lines demonstrated TF expression in vitro and in vivo. Additionally, TF expression was documented to localize to cancer cells in tumors. In vitro, TF-targeted NIR-PIT caused cell death in a light dose-dependent manner. In vivo, TF-targeted NIR-PIT suppressed tumor growth and improved survival rates compared to controls. Furthermore, in vivo NIR-PIT showed histological signs of cancer cell damage, such as cytoplasmic vacuolation, nuclear dysmorphism, and extracellular leakage of LDHA consistent with cell death. In conclusion, TF-targeted NIR-PIT holds promise as a treatment for multiple cancer models expressing TF, spanning multiple cancer types. Keywords Tissue factor · Factor III · Near-infrared photoimmunotherapy · Preclinical model Introduction Despite major advances in the treatment of cancer including antibody drug conjugates (ADCs) and immune modulatory therapies among others, new targeted treatments are still needed to eradicate most cancers [1–5] . Tissue factor (TF), also known as Factor III, CD142, or thromboplastin encoded by F3 gene, is a transmembrane glycoprotein commonly expressed on the cell surface membrane [6] . TF is a cofactor for coagulation activity factor VII/FVIIa and plays a crucial role in the coagulation cascade [7–10] . In malignancy, TF expression is often upregulated downstream of KRAS mutations and p53 inactivation, two of the most prevalent * Hisataka Kobayashi [kobayash@mail.nih.gov](kobayash@mail.nih.gov) 1 Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIH, 10 Center Drive, Bethesda, MD 20892, USA genetic alterations in human cancers [11, 12] . TF expression is, therefore, a common feature of numerous cancers [13] and has been implicated in cancer proliferation, metastasis, angiogenesis, and immune escape [6, 10, 13–17] . Thus, TFis an attractive therapeutic target for cancer treatment. Tisotsumab vedotin is an ADC that targets TF that received accelerated approval from the US Food and Drug Administration in September 2021 for the treatment of adult patients with recurrent or metastatic cervical cancer who has disease progression during or after chemotherapy [18] . Its role in other solid cancers is undergoing clinical trials (NCT03485209, NCT04697628) . ADCs are attractive because they theoretically target cance

FAQs

Why is tissue factor considered a therapeutic target in cancer?

Tissue factor is frequently expressed in cancers and is linked to key malignant processes including proliferation, metastasis, angiogenesis, and immune escape.

How was TF-targeted NIR-PIT constructed in this work?

The TF antibody Tisotumab was conjugated to the near-infrared photoabsorber IR700 to form an APC that binds cancer cells before light exposure.

What effects did TF-targeted NIR-PIT show in experiments?

In vitro, it induced light-dose-dependent cancer cell death, and in vivo it suppressed tumor growth, improved survival, and produced histological evidence consistent with cancer cell damage and death.

Sep 23, 2026

Uploaded by Jiven