Xsphera Biosciences: New Technology Tests Cancer Treatments on Live Tissue Samples

The current landscape of treatment options for solid tumors is quite limited. This is in part because many treatments that show potential in preclinical studies using mice don’t pan out when tested on humans, causing them to fail in clinical trials. Now a groundbreaking discovery that originated within the lab of David Barbie, MD, at Dana-Farber Cancer Institute is addressing this gap by providing a new way to study the microenvironment of a solid tumor in 3D while preserving the immune cells within. By utilizing excess tumor tissue from surgical resections, it is possible to measure the tumor’s response to different oncology drugs to narrow in on the option that will be most effective. Xsphera Biosciences Inc. was created to commercialize this licensed technology, which is now being utilized by pharmaceutical companies to improve pre-clinical testing and enhance their drug development efforts. It also has the potential to help guide more personalized treatment plans.  

Barbie, who serves as Director of the Lowe Center for Thoracic Oncology and Associate Director of the Belfer Center for Applied Cancer Science, both at Dana-Farber, explains that he and his colleagues have long studied the relationship between the immune system and lung cancer. “Identifying predictors of response to novel targeted and immune modulating cancer therapies has been a longstanding goal of precision cancer therapy,” he says. Severalyears ago, he realized that traditional methods of growing cancer cell lines proved inadequate to predict human response to emerging treatment methods. This led Barbie to explore a chip-like device developed by Roger Kamm, PhD, the Cecil and Ida Green Distinguished Professor with MIT Biological Engineering, that could be used to test human tissue samples outside of the body. Post-doctoral fellows Amir Aref, PhD and Russell Jenkins, MD, PhD, who is currently a medical oncologist at Medical University of South Caroline, and Cloud Paweletz, PhD, currently Head of Research for the Belfer Institute,  worked together with Barbie to develop this 3D device to test new treatments on  tumor tissue provided from consenting surgical patients at Brigham and Women’s Hospital and MGH.  

Capturing the Immune Response  

This technology enables functional precision medicine, particularly in testing combination therapies with PD-1 blockade [treatments that prevent cells from blocking the immune response against the cancer], which have largely failed in clinical trials.   

David Barbie, MD

Initially, the researchers attempted to divide the tumors into small portions to fit in the chip, but this approach was unsuccessful. They considered developing organoids, where tumors are digested into single cells and grown in 3D over months. However, the immune cells within the tumor microenvironment were lost, impairing the ability of the organoids to replicate a real-life response.   

Then Barbie had a breakthrough: he realized that partially digesting the tumor into fractions and using filters to capture tumor spheroids (40-100 microns in size) could retain the immune cells so the scientists could view them outside of the body to see how they act. This method, using collagenase and filters, successfully produced patient-derived organotypic tumor spheroids that could be used to test different treatments.  

“The retention of immune cells in the spheroids allows for dynamic measurement of tumor responses to immunotherapy, addressing the poor predictability of a patient’s response based on static biomarkers like PD-L1 levels [levels of a protein found on cells that plays a crucial role in the immune system’s response to cancer]. This technology enables functional precision medicine, particularly in testing combination therapies with PD-1 blockade [treatments that prevent cells from blocking the immune response against the cancer], which have largely failed in clinical trials,” Barbie says.   

Putting the Concept to the Test  

Barbie and his colleagues published two papers in 2018 that explored the use of the spheroid model for evaluating immune checkpoint inhibitors. The first paper, which appeared in Cancer Discovery, introduced the microfluidic system to test immune checkpoint blockade, maintaining immune components and native architecture. The second paper, which appeared in the Lab on a Chipjournal, builds upon methods of use and proposes some novel applications and future directions.  

 “Our collaboration with Dr. Barbie’s laboratory highlights the Belfer Center’s unique ability to bridge cutting-edge laboratory science with industrial-scale innovation—demonstrating how early discoveries can be rapidly transformed into real-world business opportunities,” Paweletz points out. 

Utilizing the Technology to Advance Drug Development   

In 2019, Xsphera was formed to carry the spheroid model forward into the commercial space, where it is applicable for all solid tumor cancer indications. The model is now being used by pharmaceutical companies and biotech startups, enabling them to conduct pre-clinical testing that can help predict the human response to different therapies, according to Stephen Remondi, Xsphera’s CEO and founder.  

“Our customers are using the model that originated at Dana-Farber to test multiple drugs on live spheroids from each patient’s cancerous tissue to see the vastly different responses. They can see how the tumor responds to each drug, including which pathways are being activated and what the cell populations are doing in response,” he says.  

“This gives us an unprecedented window into the tumor microenvironment. Because we’re doing this research outside the body, you can probe and destroy the cells to understand the full immune response in a way you can’t do in a clinical trial,” Remondi stresses.   

Such efforts are showing results. “We tested a drug for a startup company in our platform pretty extensively to demonstrate its mechanism-of-action, efficacy, and improved therapeutic benefit in combination with a standard-of-care drug, and now that drug has been licensed and is available to patients in clinical trials,” he says. Now, other successes are also coming down the pike, Remondi says.  

He points out that the technology will help reduce the number of clinical trials that fail by helping pharma companies select better lead candidates, narrow their focus on target indications, consider synergistic combination drug strategies, and identify patients that are most likely to benefit. This can reduce costs and accelerate drug approval, ultimately enabling patients to have more therapies to draw from. He also predicts that in the future, clinicians will also be able to use the platform to identify the drug that will most likely be effective for each patient.  

Team Members