The authors say their 3D model improves on results using traditional 2-dimensional approaches.
A new report suggests a microfluid platform could be a meaningful tool to screen potential new therapies for diffuse large B-cell lymphoma (DLBCL).
The study was based on an evaluation using the R-CHOP (rituximab [Rituxan] plus cyclophosphamide, hydroxydaunomycin, Oncovin [vincristine sulfate], and prednisone) chemotherapy regimen. The report was published in Cell Death & Disease.
R-CHOP has long been the standard of care for DLBCL. However, up to half of patients will relapse, so additional therapies are needed, said the study authors. Unfortunately, developing and testing new therapies is costly and challenging. One reason for the difficulty, they said, is that current in vitro screening models are 2D and therefore fail to accurately reflect the real-world 3D arrangement of DLBCL in a cancerous lymph node.
“Treatments that appear highly effective in vitro frequently do not translate to in vivo models or clinical success,” they said. “Utilizing 3D in vitro models to better recreate the metastatic lymph node microenvironment is therefore logical to better screen potential treatments for DLBCL before dedicating resources to in vivo models.”
Most of the previous attempts to develop a 3D model have had significant shortcomings, the authors said. But they believe their new approach can succeed.
“To create an improved platform for culturing and testing DLBCL, we applied our previously demonstrated droplet-based microfluidic spheroid model,” they wrote. “This device combines 1000 droplet docking sites with an alginate-based hydrogel to create aqueous-in-oil droplets laden with cells that can be cross-linked, continuously perfused, and imaged on-chip.”
They said one important feature of this platform is the continuous perfusion, which allows for the delivery of relevant nutrients and treatment conditions.
“In addition, this device allows for both real-time monitoring on-chip as well as downstream analysis through recollection of cells and continuous collection of secretions from the device’s array outlet,” they said.
To assess the platform, they used primary human DLBCL along with primary natural killer (NK) cells, treating them with rituximab, CHOP, or a combination of both. They said they chose to add NK cells because they can function independently of antigen-presenting cells and they are the most prominent immune cells in the DLBCL microenvironment.
The authors evaluated several criteria, including cellular viability in response to treatment, rheological properties, and cell surface marker expression levels to see if their results would match what would be expected in vivo. They also measured changes in cellular secretions and transcriptomics.
“Our results showed complex changes in phenotype and transcriptomic response to treatment stimuli, including numerous metabolic and immunogenic changes,” they said. “These findings support this model as an optimal platform for the comparative screening of novel treatments.”
Moreover, they said said their model helps explain problems with traditional plate assays. For instance, they said the level of efficacy observed when samples were treated with rituximab alone was much higher in their plate assays than what has been seen in clinical data.
“These results may be influenced by the drastically reduced expression of CD20 in spheroids compared to expression seen in DLBCL cells taken directly from culture…” they said. “Ultimately, these findings suggest a traditional plate assay produces data that contradicts clinical responses and is less reproducible than our 3D model.”
The investigators said their findings are important because they suggest that it could be possible to more accurately screen and tailor potential novel immunotherapies with results that are much more reliable than current 2D models.
“Given the extensive variety of novel therapies and combinatorial approaches for treating lymphoma, enhanced models for early screening are essential to expedite and improve the quality of early drug,” they said.
Reference
Sullivan MR, White RP, Dashnamoorthy Ravi, et al. Characterizing influence of rCHOP treatment on diffuse large B-cell lymphoma microenvironment through in vitro microfluidic spheroid model. Cell Death Dis. Published online January 9, 2024. doi:10.1038/s41419-023-06299-6
AA Unlikely to Cause Anxiety, Depression but May Be Affected by Mental Illness
May 7th 2024A Mendelian randomization study using genetic analysis found that alopecia areata (AA) increases the risk of anxiety and depression, but not the other way around, providing unique evidence for a causal link while adding to existing evidence.
Read More
Examining Low-Value Cancer Care Trends Amidst the COVID-19 Pandemic
April 25th 2024On this episode of Managed Care Cast, we're talking with the authors of a study published in the April 2024 issue of The American Journal of Managed Care® about their findings on the rates of low-value cancer care services throughout the COVID-19 pandemic.
Listen
AUA Session Highlights the General Urologist’s Role in Gender-Affirming Care
May 7th 2024During her session, Polina Reyblat, MD, Kaiser Permanente Los Angeles Medical Center, highlighted best practices urologists should incorporate to make transgender and gender-diverse patients comfortable during physical exams and avoid retraumatization.
Read More
Navigating Health Literacy, Social Determinants, and Discrimination in National Health Plans
February 13th 2024On this episode of Managed Care Cast, we're talking with the authors of a study published in the February 2024 issue of The American Journal of Managed Care® about their findings on how health plans can screen for health literacy, social determinants of health, and perceived health care discrimination.
Listen
Access Denied: CMS’ Action Hurts Patients With Cancer in Rural America
May 6th 2024CMS rules hindered the access of rural patients with cancer to medically integrated pharmacies in 2023. The authors discuss the impact on equity in health care, emphasizing the need for regulatory change.
Read More
What Mass General Brigham Is Doing to Combat Prostate Cancer Disparities Among Men of Color
May 5th 2024Quoc-Dien Trinh, MD, MBA, chief of urology at Brigham & Women's Faulkner Hospital, highlighted successful efforts to improve prostate cancer care access for underserved communities in Massachusetts.
Read More