ML7710 for photoimmunotherapy against regulatory T cells in tumors

Customer case

The Laboratory of Molecular Theranostics is a major research section of the Molecular Imaging Program at National Cancer Institute (NCI) and is led by Dr. Hisataka Kobayashi. The groundbreaking research includes the development of imaging and theranostic probes, which can aid in cancer detection and treatment. Dr. Kobayashi has invented near-infrared photoimmunotherapy (NIR-PIT) with IRDye700DX, which has been commercialized by Rakuten Medical and was approved in Japan in 2020 and is currently in FDA-designated fast-track global Phase 3 trials for inoperable Head & Neck cancer.

Dr. Hisataka Kobayashi M.D., PhD

 

Dr. Peter L. Choyke M.D., PhD

 

 

Modulight products: ML7710 (multiple channels on 689 nm, 2 W)

Laser use: High-throughput in vivo illumination to study photoimmunotherapy of cancer targeted against various molecular targets including EGFR, HER2, CTLA-4, and CD25. Multi-channel ML7710 laser system was used to illuminate multiple test subjects in parallel enabling controlled and high-throughput in vivo experiments.

Link to the study:

 

Background

Body’s immune system detects and destroys abnormal cells and prevents the growth of cancers as part of its normal function. However, cancers often develop strategies to evade or suppress immune system so that they can continue growing without being destroyed. Cancer immunotherapies, such as immune checkpoint inhibition or CAR T cell therapy, help the patient’s own immune system to fight these cancers. Immunotherapies have achieved dramatic clinical success during the past decade and resulted in lasting remissions even in cancer patients that were previously considered terminally ill.

One key immunotherapy strategy is to eliminate immune suppressor cells such as regulatory T cells (Tregs) from the tumors. Typically a large number of Tregs infiltrate cancers and their presence correlates with a poor prognosis. These cells prevent tumor-infiltrating killer T cells from destroying the tumor and depletion of Tregs might result in tumor regression through activation and amplification of killer T cells. CD25 is a highly expressed target molecule on the surface of Tregs and could be targeted with immunotherapy to selectively eliminate these cells.

Near-infrared photoimmunotherapy (PIT) is a novel type of immunotherapy that utilizes photoabsorber IRDye700DX conjugated to tumor cell-targeting antibody. The photoactive component is then activated with near-infrared (NIR) light at 689 nm to induce the therapeutic response. This therapy modality has been shown to be effective in directly targeting cancer cells while targeting tumor microenvironment such as Tregs could be applicable to many different tumor types and become a versatile cancer therapy.

 

Study description

The goal was to design an effective photoimmunotherapy against tumor-promoting Tregs for cancer treatment. The problem with using an antibody (IgG) for targeting CD25 on Tregs is that this can also block interleukin-2 (IL-2) cytokine from binding and activating killer T cells, which might undesirably decrease antitumor immune responses. This problem might be avoided by using small antibody fragments F(ab´)2 against CD25 that have much faster clearance from the circulation and this way less opportunities to suppress the beneficial killer T cells. The efficacy of photoimmunotherapy was evaluated in vivo using either full IgG or F(ab’)2 fragments against CD25. Tumor growth, survival times, and number of killer T cells were monitored after the treatment.

 

 

The above schematics are reproduced from the original publication.

 

Results

Tumor growth was significantly suppressed by photoimmunotherapy, compared to control or IgG without light activation. Tumor growth suppression as well as overall survival after photoimmunotherapy were significantly better with F(ab´)2 fragments than with full IgG. This efficacy improvement might be related to killer T cells, which were detected in much higher numbers after photoimmunotherapy with F(ab´)2 fragments and are key cells for the generation of efficient systemic antitumor immunity.

 

Tumor growth between study groups

 

Survival between study groups

 

Graphs are reproduced according the original publication.

 

 

Conclusions:
Anti-CD25 targeted photoimmunotherapy against tumor-infiltrating Tregs demonstrated superior efficacy in vivo when F(ab’)2 antibody fragments were used compared to full IgG antibody. Photoimmunotherapy with F(ab´)2 fragments has also potential to effectively eradicate tumors elsewhere in the body through enhanced activation of killer T cells. In future, efficacy might be further increased by combining this tumor microenvironment-targeted strategy with conventional photoimmunotherapy that directly targets the cancer cells.

 

Related Modulight products and Services

 

Related Publications

The Effect of Antibody Fragments on CD25 Targeted Regulatory T Cell Near-Infrared Photoimmunotherapy
Ryuhei Okada, Yasuhiro Maruoka, Aki Furusawa, Fuyuki Inagaki, Tadanobu Nagaya, Daiki Fujimura, Peter L. Choyke, Hisataka Kobayashi
Bioconjug Chem, 2019, 30 (10)

 

 

 

Contact Us

Do you have questions or comments related to this application note? Maybe you would like to request literature? Or would you like us to feature your research? Please drop us a line!

    First name *

    Family name *

    Company or affiliation *