Broadly-applicable imaging platforms are necessary for optimizing cell therapies in solid tumorsPublished: July 22, 2019
Meeting Preclinical Data Requirements For Cell & Gene Therapies
D Morrow, M Srinivas, C Mann, A Ussi & AL Andreu
The introduction of immunotherapy, particularly immune cell therapies, have transformed the therapeutic landscape in recent years. Cell therapies are now finally reaching patients in growing numbers, with many more set to come through the pipeline in the next few years. In 2017, Novartis’s Kymriah® received FDA approval for patients up to 25 years with acute lymphoblastic leukemia (ALL) that has either relapsed or is refractory. This approval followed the near extraordinary results of the case of Emily Whitehead, a 7-year-old girl who had been fighting ALL for more than a year, whose cancer went in to remission following treatment. Emily is now 6 years cancer-free. In the months that followed Kymriah’s® approval, two other gene therapies joined the market: Yescarta®, a CAR T-cell therapy marketed by Gilead to treat certain types of large B-cell lymphoma; and Luxturna®, Spark Therapeutics’ gene therapy for a rare form of inherited vision loss. Although these three therapies would be the first, they will certainly not be the last, with over 900 cell and gene therapy-related clinical trials in planning phase or ongoing, according to www.ClinicalTrials.gov. Following the success of Kymriah®, all eyes now turn towards large patient groups with solid tumor cancers and whether the success of CAR-Ts can be reproduced in these patients. However, solid tumors represent a much greater challenge. These tumors incorporate mechanisms designed to keep T cells out, due to the tumor microenvironment where any cell and gene therapy would need to incorporate a strategy to overcome the tumor’s blocking mechanism. To date, a strategy for this simply does not exist, and before any such strategy can be comprehensively evaluated in vivo, a means to track these cells in situ and subsequently monitor their success is fundamental. This strategy could develop a first in class prognostic indicator that can follow the localization or proliferation of these cells. Stratifying responders versus non-responders for cell therapies could be achieved at the clinic through effective cell tracking as the healthcare industry now embraces the clear clinical benefits of the personalized medicine approach. For the clinician and scientist to understand these cell therapies in greater detail, we need to measure the function and behavior of these cells when delivered to the patient. What are the cells doing? Where do they go after being administered to the patient? This commentary piece focuses on the pressing need to develop a broadly applicable platform that incorporates in vivo imaging and modelling for the optimization of cell therapies, that can be integrated in existing cell therapy supply chains. This platform requires a collaboration of the imager, the preclinical scientist, the regulator, manufacturer and the clinician to make it functional for optimizing the cell therapies in solid tumors. If successful, the platform should be robust enough to be rolled out at any clinical site and be adaptable to any cell therapy type.DOI: 10.18609/cgti.2019.071
Citation: Cell & Gene Therapy Insights 2019; 5(7), 629-638.