2 research outputs found
Fast Image-Guided Stratification Using Anti-Programmed Death Ligand 1 Gold Nanoparticles for Cancer Immunotherapy
Cancer
immunotherapy has made enormous progress in offering safer
and more effective treatments for the disease. Specifically, programmed
death ligand 1 antibody (αPDL1), designed to perform immune
checkpoint blockade (ICB), is now considered a pillar in cancer immunotherapy.
However, due to the complexity and heterogeneity of tumors, as well
as the diversity in patient response, ICB therapy only has a 30% success
rate, at most; moreover, the efficacy of ICB can be evaluated only
two months after start of treatment. Therefore, early identification
of potential responders and nonresponders to therapy, using noninvasive
means, is crucial for improving treatment decisions. Here, we report
a straightforward approach for fast, image-guided prediction of therapeutic
response to ICB. In a colon cancer mouse model, we demonstrate that
the combination of computed tomography imaging and gold nanoparticles
conjugated to αPDL1 allowed prediction of therapeutic response,
as early as 48 h after treatment. This was achieved by noninvasive
measurement of nanoparticle accumulation levels within the tumors.
Moreover, we show that the nanoparticles efficiently prevented tumor
growth with only a fifth of the standard dosage of clinical care.
This technology may be developed into a powerful tool for early and
noninvasive patient stratification as responders or nonresponders
Nanomedicine for Cancer Immunotherapy: Tracking Cancer-Specific T‑Cells <i>in Vivo</i> with Gold Nanoparticles and CT Imaging
Application of immune cell-based therapy in routine clinical practice is challenging due to the poorly understood mechanisms underlying success or failure of treatment. Development of accurate and quantitative imaging techniques for noninvasive cell tracking can provide essential knowledge for elucidating these mechanisms. We designed a novel method for longitudinal and quantitative <i>in vivo</i> cell tracking, based on the superior visualization abilities of classical X-ray computed tomography (CT), combined with state-of-the-art nanotechnology. Herein, T-cells were transduced to express a melanoma-specific T-cell receptor and then labeled with gold nanoparticles (GNPs) as a CT contrast agent. The GNP-labeled T-cells were injected intravenously to mice bearing human melanoma xenografts, and whole-body CT imaging allowed examination of the distribution, migration, and kinetics of T-cells. Using CT, we found that transduced T-cells accumulated at the tumor site, as opposed to nontransduced cells. Labeling with gold nanoparticles did not affect T-cell function, as demonstrated both <i>in vitro</i>, by cytokine release and proliferation assays, and <i>in vivo</i>, as tumor regression was observed. Moreover, to validate the accuracy and reliability of the proposed cell tracking technique, T-cells were labeled both with green fluorescent protein for fluorescence imaging, and with GNPs for CT imaging. A remarkable correlation in signal intensity at the tumor site was observed between the two imaging modalities, at all time points examined, providing evidence for the accuracy of our CT cell tracking abilities. This new method for cell tracking with CT offers a valuable tool for research, and more importantly for clinical applications, to study the fate of immune cells in cancer immunotherapy