한빛사 인터뷰
1. You recently published a paper, in the journal “Sci. Transl. Med. (2020), titled “Effective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors”.
-Can you please briefly summarize this paper?
Chimeric antigen receptor (CAR) T cell therapy has shown remarkable therapeutic efficacy against hematological malignancies, but it has not translated into the treatment against solid tumors. The major challenges include: 1) accessibility of tumor specific antigens that will minimize on-target off-tumor toxicities, 2) antigen heterogeneity leading to tumor escape, and 3) immunosuppressive tumor microenvironment comprised of both cellular and structural factors. We used a combinatorial approach using two immunotherapeutic agents to address these challenges. Our oncolytic virus was engineered to express truncated CD19 (CD19t), which was used to not only deliver a target, but to also infect tumor cells allowing for favorable changes to the tumor microenvironment. We have successfully used our oncolytic virus to infect and deliver CD19t as a target for our CD19-CAR T cells. The combination demonstrated enhanced infiltration of CAR and endogenous T cells into the solid tumor space leading to significantly greater anti-tumor activity.
- Can you please tell us the main difficulties you had in the laboratory work and how you overcame them?
Engineering murine CAR T cells with high transduction efficiency was difficult to achieve since T cells isolated from mouse splenocytes are sensitive and challenging to work with. We had to figure out the best vector and virus to use. It was also quite difficult to figure out the dose of oncolytic virus to treat mice with and the timing of CAR T cell treatment, especially in the syngeneic mouse model. We overcame this difficulty by repeating the in vivo study multiple times, which required a lot of work and time.
2. Please introduce your laboratory, university or organization to bio-researchers in Korea.
I am a part of two programs at City of Hope National Medical Center: the T Cell Therapeutics Research Laboratory (TCTRL) in the department of Hematology and Hematopoietic Cell Transplantation led by Dr. Stephen J. Forman under the guidance of Dr. Saul Priceman, and the Oncolytic Viral Therapy Laboratory in the department of Surgery led by Dr. Yuman Fong. City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hope’s translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope has been ranked among the nation’s “Best Hospitals” in cancer by U.S. News & World Report for 14 consecutive years. Its main campus is located near Los Angeles, with additional locations throughout Southern California. City of Hope is a great place to do translational research, especially in cancer immunotherapy. We have many post-doctoral fellows and visiting scientists from Korea at our institution. We currently have one post-doctoral fellow who came from KAIST working in our lab.
3. Please tell us your experiences and your thoughts related to research activities abroad.
I received by Bachelor of Science degree from the University of California San Diego (UCSD) where I worked in the laboratory of Dr. Ethan Bier investigating various human diseases using Drosophila as a model. Then I worked as a student in the CIRM Bridges Graduate Internship Program at City of Hope, and continued on as a graduate student to obtain my Ph.D. Doing research in the U.S. has been great with abundant funding and grants available along with many networking events such as conferences. Coming to the U.S. to do research would be a great opportunity to learn in a new environment and improve your English writing and speaking skills.
4. Can you provide some advice for younger scientists who have plans to study abroad?
The most important factor for scientists who want to study abroad is finding a mentor that is the right fit for your work style and personality. The best way to find out is by contacting members of the lab with varying positions to learn and understand what it is like working in that particular lab.
5. Future plan?
We are planning to start a clinical trial within the next two years using this combination immunotherapy. Additionally, we are working on other exciting projects, and we hope to publish in high impact journals in the near future. I also plan to start a company using the technologies that we have developed.
6. Do you have anything else that you would like to tell Korean scientists and students??
Please feel free to contact me if you have any questions about our work, and any questions regarding City of Hope.
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