Assessing the efficacy of NIR duocarmycin photorelease with the PRISM in vivo photon counting system

A recent study by Kobayashi et al. has shed new light on the potential of combining near-infrared duocarmycin photorelease (NIR-DPR) with PD-1 blockade to improve cancer treatment outcomes. At the heart of this groundbreaking research is MediLumine’s PRISM imaging system, which played a crucial role in uncovering these new insights.

The Role of Tregs in Tumor Immunosuppression

Regulatory T cells (Tregs) are key players in the tumor microenvironment, known for their ability to mediate immunosuppression and hinder the effectiveness of PD-1 blockade immunotherapy. While targeting Tregs presents a promising therapeutic strategy, systemic depletion of these cells can lead to severe autoimmune side effects. This has posed a significant challenge for researchers aiming to develop Treg-directed therapies.

Innovative Solution: CD25-Targeted NIR-DPR from Dr. Kobayashi’s Laboratory using the PRISM In Vivo Imaging System

The study introduces a novel approach to selectively target Tregs within the tumor microenvironment using CD25-targeted NIR-DPR. This technology involves the use of anti-CD25 F(ab’)2 conjugates that specifically uncage duocarmycin in CD25-expressing cells upon exposure to NIR light. The result is a localized and predominant damage to Tregs, sparing other immune cells and reducing the risk of autoimmune complications.

The PRISM’s Imaging System was used to visualize the biodistribution of CD25-CyPeg-Duo in vivo and monitor tumor growth with bioluminescent imaging of the luciferase reporter. Here are more details the PRISM In Vivo Imaging system was used:

1. Fluorescent Imaging: Changes in 800-nm fluorescence intensity at the tumor site were meticulously recorded before and after treatment. This data provided crucial insights into the effectiveness of CD25-targeted NIR-DPR in reducing intratumoral CD25+ Treg populations.
2. Bioluminescence Imaging: The PRISM system enabled precise measurement of luciferase activity in MB49-luc tumor models. The results highlighted significant reductions in luciferase activity post-treatment, indicating successful targeting of Tregs.
3. Tumor Growth Monitoring: The system’s high sensitivity allowed for accurate tracking of tumor growth curves, demonstrating the synergistic effect of combining CD25-targeted NIR-DPR with PD-1 blockade. This combination therapy not only suppressed tumor growth but also improved overall survival in murine models.

Full Citation:

Hiroshi Fukushima, Aki Furusawa, Seiichiro Takao, Ebaston Thankarajan, Michael P Luciano, Syed Muhammad Usama, Makoto Kano, Shuhei Okuyama, Hiroshi Yamamoto, Motofumi Suzuki, Miyu Kano, Peter L Choyke, Martin J Schnermann & Hisataka Kobayashi (2024) Near-infrared duocarmycin photorelease from a Treg-targeted antibody-drug conjugate improves efficacy of PD-1 blockade in syngeneic murine tumor models, OncoImmunology, 13:1, DOI: 10.1080/2162402X.2024.2370544