Immuno-Oncology Imaging

Our mission is to create a novel medical imaging methodology using near-infrared light and advance our understanding of immunology and immunotherapy. Our central focus has been to develop a new imaging technology to dissect the immune response in the context of cancer, allergy, and infectious diseases with the ultimate goal of translating the knowledge into clinical practice. For example, our group successfully established (1) near-infrared imaging technology of immune components including vaccines and exosomes to improve immunotherapy and (2) molecular imaging of cancer signaling to develop a novel targeted cancer therapy. We are also working to establish safe, effective, simple, and affordable immunotherapy for infectious diseases, allergies, autoimmune diseases, and cancer using near-infrared laser technology.

1. Immunotherapy imaging

Once a vaccine or immunotherapeutic is injected, it has to reach the right location called “secondary lymphoid tissue” to be effective. However, there is no non-invasive method to describe its behavior in a real-time manner. We are solving this issue to create a reliable monitoring strategy for vaccine or immunotherapeutic imaging using renal clearable zwitterionic near-infrared fluorophores with high target-to-background ratios. Recently, we demonstrated the size-dependent transportation of vaccine from the injection site to the secondary lymphoid tissues using a multispectral near-infrared imaging platform. In this program, we aim to develop a novel technology that can be used to optimize formulation and evaluate the safety of vaccines and immunotherapeutics.

2. Immuno-oncology imaging

Pre- and post-operative and intraoperative cancer imaging is critical for the management of cancer patients. However, traditional imaging including CT, MRI, and ultrasound is not good enough to precisely describe the location of small cancers. We are solving this issue by creating a high-sensitive and specific imaging modality. Recently, we established a reliable imaging method with a high signal-to-background ratio using TLR4 antibody conjugated with a renal clearable zwitterionic near-infrared fluorophore. In this project, we were able to image liver cancer in real-time after a single intravenous injection of TLR4-targeted near-infrared fluorophores over 3 days under the NIR fluorescence imaging system. The probe was determined to target tumor-associated macrophages resulting in specific imaging of liver cancer which is enriched with tumor-associated macrophages. This method can be further extended for intraoperative imaging of many types of cancer.

3. Laser adjuvant technology

To boost the immune system, we have been traditionally using chemicals and biologicals. However, they may induce adverse effects. We are working to create a novel solution using “laser light”. Recently, we have shown that skin treatment with near-infrared laser light boosts the immune response to vaccines. This “laser adjuvant” has numerous advantages over the historical chemical or biological agents; it is free from cold-chain storage, hypodermic needles, biohazardous sharp waste, irreversible formulation with vaccine antigen, undesirable biodistribution in vital organs or unknown long-term toxicity. In addition, laser technology has been used in the clinic for more than three decades and is therefore technically matured and safe. Since vaccine formulations are given to healthy populations, these characteristics render the “laser adjuvant” significant advantages for clinical use and open a new developmental path for a safe and effective vaccine.

4. Immune-function imaging

Real-time assessment of immune cell function is challenging. In order to resolve this issue, we recently developed a new optical platform equipped with two distinct wavelengths of lasers to realize high-throughput single cell live immune cell imaging. Using this technology, we successfully observed mitochondrial retrograde signaling including intracellular calcium and reactive oxygen species (ROS) in a large number of T cells simultaneously. This technology could be further used to study the function of other types of immune cells.

Relevant Publications

1. Kimizuka Y, Katagiri W, Locascio JJ, Shigeta A, Sasaki Y, Shibata M, Morse K, Sîrbulescu RF, Miyatake M, Reeves P, Suematsu M, Gelfand J, Brauns T, Poznansky MC, Tsukada K, Kashiwagi S. (2018) J Immunol. 201(12):3587-3603. PMID: 30420435. PMCID: PMC6289684.

2. Katagiri W, Lee JH, Tétrault M-A, Kang H, Jeong S, Yokomizo S, Santos S, Jones C, Hu S, Tsukada K, Fakhri G, ChoiHS, Kashiwagi S. (2019) Real-time imaging of vaccine biodistribution using zwitterionic NIR nanoparticles. Adv Healthcare Mater. e1900035. PMID: 31165556. PMCID: PMC6687515.

3. Ji Y, Wang Z, Bao K, Park GK, Kang H, Hu S, McDonald E, Kashiwagi S,*Choi HS.* (2019) Targeted molecular imaging of TLR4 in hepatocellular carcinoma using zwitterionic NIR fluorophores. Quant Imaging Med Surg. 9(9):1548-1555. PMID: 31667140. PMCID: PMC6785503 *corresponding author.

4. Katagiri W, Lee G, Tanushi A, Tsukada K, Choi HS, Kashiwagi S. (2020) High-throughput single-cell live imaging of photobiomodulation with multispectral near-infrared lasers in cultured T cells. J Biomed Opt. 25(3):1-18. PMID: 32193907. PMCID: PMC7081057.

5. Ji Y, Jones C, Baek Y, Park GK, Kashiwagi S,*Choi HS.* (2020) Near-infrared fluorescence imaging in immunotherapy. Adv Drug Deliv Rev. S0169-409X(20)30058-2. PMID: 32579891. 

6. Kashiwagi S. (2020) Laser adjuvant for vaccination. FASEB J, 34(3):3485-3500. PMID: 31994227. PMCID: PMC7060115.

7. Hailey Monaco, Shinya Yokomizo, Haksoo Choi, and Satoshi Kashiwagi. 5/2022. Quickly evolving near-infrared photoimmunotherapy provides multifaceted approach to modern cancer treatment. VIEW, 3, 3, Pp. 20200110.

8. Kang H, Kang MW, Kashiwagi S*, Choi HS*. NIR fluorescence imaging and treatment for cancer immunotherapy. J Immunother Cancer 2022;10(7):e004936. PMCID: PMC9305898.

9. Katagiri W, Lee GH, Tanushi A, Tsukada K, Choi HS*, Kashiwagi S*. Dual near-infrared II laser modulates the cellular redox state of T cells and augments the efficacy of cancer immunotherapy. FASEB J, 36, Pp. e22521. PMCID: PMC9574655.

 Research Team

Leader: Satoshi Kashiwagi, M.D., Ph.D., Assistant Professor of Radiology

Members

• Haesang Park, M.D., Ph.D., Visiting Assistant Professor

• Shinya Yokomizo, Ph.D., Postdoctoral research fellow

• Jiyun Rho, B.S., Visiting graduate student

• Hailey Monaco, B.S. Candidate, Research Student

• Hajin Joanne Kim, B.A., Research Assistant

• Rose McDonnell, B.S. Candidate, Research Student