Immunotherapy is gaining traction as a prominent approach to cancer treatment. These therapies encompass the use of Chimeric Antigen Receptor-engineered T-cells (CAR T-cells), tumor-infiltrating lymphocytes (TILs) and other genetically modified T-cells to specifically target cancer cells.
Image Credit: CI Photos/Shutterstock.com
While significant progress has been made with immunotherapy for blood cancers, its effectiveness in treating solid tumors remains limited.
A key factor contributing to this low success rate is the solid tumor microenvironment (TME), where suppressive cytokines hinder the tumor-killing capacity of T-cells. Therefore, it is imperative to understand the role of the TME in T-cell responses to develop more effective cancer therapies.
The advantages of using three-dimensional (3D) patient-derived organoids (PDOs) stem from their ability to replicate the physical and chemical cues of the tumor microenvironment (TME)—factors that are absent in traditional 2D monolayer cultures.
Research indicates that PDOs respond to drugs in ways that closely mirror the responses of the original tumors, highlighting their potential to improve therapeutic outcomes.
As physiologically and pathologically relevant cancer models, PDOs better capture the key characteristics of primary tumors. This makes them a more suitable platform than 2D models for evaluating the effectiveness of T-cell–mediated killing.
Despite the advantages associated with PDOs, substantial obstacles hinder their widespread implementation in drug discovery. The production of organoids is a costly and labor-intensive endeavor. Furthermore, organoid culture requires specialized manual skills, leading to significant variability among operators.
To address the challenges associated with large-scale applications of PDOs, a semi-automated bioprocess has been developed for the large-scale expansion of assay-ready organoids.
In the study discussed here, a method to evaluate T-cell invasion in solid tumors using PDOs was devised.
Utilizing bioreactor-expanded patient-derived colorectal cancer organoids (CRCs), activated human peripheral blood mononuclear cells (PBMCs) were stained with CellTracker and introduced to CRCs (stained with MitoTracker) in a 96-well microtiter plate, with monitoring occurring every four hours for three days via a high-content imager.
To quantify T-cell invasion, an image analysis method to measure the distance of each T-cell to the nearest organoid was established. The findings indicated that stimulated T-cells demonstrated a shorter interaction distance compared to non-stimulated T-cells. These results highlight the utility of bioreactor-expanded organoids in large-scale T-cell-based screening assays.
Download the App Note
Acknowledgments
Produced from materials originally authored by Zhisong Tong and Angeline Lim from Molecular Devices.
About Molecular Devices UK Ltd 
Molecular Devices is one of the world’s leading providers of high-performance life science technology. We make advanced scientific discovery possible for academia, pharma, and biotech customers with platforms for high-throughput screening, genomic and cellular analysis, colony selection and microplate detection. From cancer to COVID-19, we've contributed to scientific breakthroughs described in over 230,000 peer-reviewed publications.
Over 160,000 of our innovative solutions are incorporated into laboratories worldwide, enabling scientists to improve productivity and effectiveness – ultimately accelerating research and the development of new therapeutics. Molecular Devices is headquartered in Silicon Valley, Calif., with best-in-class teams around the globe. Over 1,000 associates are guided by our diverse leadership team and female president that prioritize a culture of collaboration, engagement, diversity, and inclusion.
To learn more about how Molecular Devices helps fast-track scientific discovery, visit www.moleculardevices.com.
Sponsored Content Policy: News-Medical.net publishes articles and related content that may be derived from sources where we have existing commercial relationships, provided such content adds value to the core editorial ethos of News-Medical.Net which is to educate and inform site visitors interested in medical research, science, medical devices and treatments.