Nanoparticle-augmented image-guided CAR T therapy and post-treatment assessment - SUMMARY
This proposal describes a five-year career development program to prepare the candidate, Dr. Jinhwan Kim, for
a career as an independent investigator. This program will build on Dr. Kim’s background as a material scientist
and nanobiomaterial engineer by providing additional expertise in medical imaging, cell engineering, and
nanomaterials. The primary mentor, Stanislav Emelianov, Ph.D. (Professor of BME at Georgia Tech), has
expertise in instrumentation, imaging systems and algorithms, image-guided therapy, and imaging contrast
agents. Co-mentors are Younan Xia, Ph.D. (Professor of BME at Georgia Tech), who has expertise in
nanoparticles and Gabriel Kwong, Ph.D. (Associate Professor of BME at Georgia Tech), whose expertise in T
cell engineering. Dr. Kim will collaborate with Kevin Kalinsky, M.D. (Associate Professor of Medicine at Emory
University) on breast cancer oncology, Haydn Kissick, Ph.D. (Assistant Professor of Urology at Emory University)
on cancer immunology, and Krishnendu Roy, Ph.D. (Professor of BME at Georgia Tech) on T cell manufacturing.
In this application, Dr. Kim will demonstrate the use of plasmonic nanoparticles with tunable peak optical
absorption as contrast agents for the combined ultrasound and photoacoustic (US/PA) imaging. The developed
imaging agents and US/PA system will be used for image-guided chimeric antigen receptor (CAR) T cell therapy
in breast cancer and sensing the activity of delivered CAR T cells in the tumor microenvironment (TME). Current
approaches in CAR T cell therapy lack the ability to monitor the location and activity of the infused CAR T cells
in real-time, which is critical to understand the biological effect of CAR T cells and to predict the treatment
outcome. By labeling CAR T cells with gold nanorods (AuNRs) absorbing in near-infrared (NIR) spectral range,
this project aims to enable tracking of the CAR T cells after infusion for image-guided therapy (Aim 1).
Implementing the US/PA imaging technique will allow the real-time, high-resolution detection of the CAR T cells
with great anatomical information in reliable imaging depth (Aim 2). Furthermore, the design of the gold
nanoparticle-based US/PA imaging sensors that selectively and sensitively detect cytokines released from
injected CAR T cells will enable monitoring CAR T cell activity, thereby assessing and controlling the
microenvironment with additional external stimulation (Aim 3). Aims 1 and 2 (K99 phase) will be guided under
the strong mentorship from mentor/co-mentors with extensive training on nanotechnology (Younan Xia, Ph.D.),
CAR T cell engineering (Gabriel Kwong, Ph.D.), and US/PA imaging (Stanislav Emelianov, Ph.D.). Dr. Kim will
independently conduct the proposed aim 3 with the extended expertise gathered during the K99 phase. The
multidisciplinary knowledge gained during the overall research and career training, this project will provide a
foundation for Dr. Kim – an independent investigator in the R00 phase, to develop advanced applications of
nanotechnology in innovative therapeutic approaches to treat cancer and other diseases.
