Could smart additives improve yield across the entire bioprocessing industry, decrease the cost of biopharmaceuticals, increase the quality and safety of cell therapies, and even help to reduce and minimize animal testing? It could if they are Xheme Multifunctional Additives.
Great news for both the bioprocessing industry and the healthcare consumers it serves: The Xheme Multifunctional Additives (XMA), a programmable non-toxic nanoporous microparticle-based materials, has demonstrated the ability to significantly reduce or eliminate the damage of oxidative stress in bioproduction conditions. With its $21.9 billion market size, the bioprocessing industry plays a crucial role in delivering life-saving biopharmaceuticals and biotherapeutics to patients worldwide. However, the manufacturing of these therapies is challenging, leading to reduced yields and increased costs. An imbalance of free radicals and antioxidants known as oxidative stress regularly reduces the yield of pharmaceuticals and therapeutics produced via bioprocessing by about 10-15%.
That is where the unique technology of XMA comes in. As non-toxic, programmable nanoporous microparticle-based additives with antioxidant and antimicrobial properties, XMA acts as a scavenger of reactive oxygen species (ROS, here primarily extracellular hydrogen peroxide, H2O2), reducing the damage to cells during bioprocessing. In addition, hydrogen peroxide is an signaling molecule that increases inflammatory cytokines and alters gene expression impacting protein glycosylation and other post-translational modifications critical for antibody production in eucaryote cell culture.
Impact on Bioproduction
In testing conducted by the Institute for Applied Life Sciences’ Cell Culture Core Facility at UMASS Amherst and O2M Technologies, XMA demonstrated superior performance to current bioprocessing antioxidants.
“We developed and executed methods that explored high and low levels of XMA powders under growth conditions similar to bioproduction,” said Michael Daley, Cell Culture Director at UMass Institute for Applied Life Sciences, which provided hands-on technical expertise in evaluating the effect of the additives.
“The XMA-incorporated polyethylene film showed the ability to significantly increase cell viability by about 15% compared to the control after 48 hours,” continued Mrignayani Kotecha, PhD, Founder and CEO of O2M Technologies, an oxygen imaging company located in Chicago.
Additionally, XMA particles demonstrated a dose-dependent enhancement of cell proliferation of roughly 50%. The additive also has antibacterial activity, protects against gamma, x-ray, and UV radiation, and exhibits excellent biocompatibility with cells, leading to improved upstream bioprocessing results.
“These findings suggest that XMA-based cell culture media, bioprocessing bags, and trays will increase the yield and quality of the biologics produced,” concluded Daley.
“XMA are unlike any other additives being used in bioprocessing today,” explained Kumar Challa, Co-Founder, President, and Chief Scientific Officer of Xheme. “Unlike current anti-oxidants, which are either free-radical scavengers or remove peroxides, XMAs are holistic—performing both functions. XMAs are also regenerative, which other anti-oxidants are not, meaning less needs to be used for a better result.”
“The increase in yield and quality could result in lower bioprocessing cost, which could then be passed on to consumers as savings.”
Advancing Drug Discovery and Cell Therapies
In addition to its impact on bioproduction, XMA holds great promise in accelerating drug discovery and reducing animal testing, aligning with the global trend of seeking alternatives to animal models. 3-D organoids, grown from human and animal organ tissues, have gained traction in drug development due to their ability to replicate laboratory animal responses and simulate human body environments. However, oxidative stress and inadequate oxygenation of interior cells pose significant challenges to the widespread adoption of 3-D constructs or such as organoids or more basic spheroids which do not include stems cells.
XMA offers a potential solution to these obstacles for modern biological models that bridge the gap between in vitro preclinical development and animal testing by enabling 3-D bio-constructs that possess high physiological significance and greatly enhance drug development By adding XMA to tissue culture equipment or directly into the growth matrix, oxidative stress can be dramatically reduced, even in perfusion models that enable the interior cells to be adequately oxygenated.
“Using hydrogen peroxide to cause oxidative stress in a cellular model,” said Riccardo Amorati, PhD, an Associate Professor in the Department of Chemistry at the University of Bologna, Italy, who has worked with Xheme on previous studies, “We showed that XMA-incorporated films converted damaging peroxides into oxygen and water.”
This breakthrough for non-enzymatic reduction of oxidative stress can be expected revolutionize the rapidly growing $5.6 billion 3-D organoid industry and expedite the development of safer and more effective therapies.
Furthermore, the studies on HEK293F and human blood cells showed that XMA is not toxic in large doses, up to a concentration of 10,000µM and 100µM, respectively. Further testing is underway to determine potential toxicity, if any, at higher concentrations.
Revolutionary Potential
The XMA breakthrough technology could bring about significant changes in the industry, benefiting both healthcare consumers and manufacturers.
“What strikes me about Xheme technology is it’s remarkable versatility. As a potent catalyst and antioxidant agent, it holds potential for applications across various industries, making a significant impact on the bioprocessing field as well,” said Julia Rashba-Step, a veteran The programmable nature of Xheme additive allows for fine-tuning tailored to the specific needs of each application. In bioprocessing, this feature has proven to be particularly valuable, leading to enhanced cell viability and improved yield.”
Lowering the cost of bioprocessing and the development of cell therapies through XMA could result in more affordable life-saving treatments for patients. Additionally, the improved quality and safety of therapies produced with XMA could profoundly impact the outcomes of various conditions treated with cell therapies, including spinal cord injuries, diabetes, Parkinson’s disease, Alzheimer’s disease, heart disease, stroke, burns, cancer, and osteoarthritis. As biological therapies from monoclonal antibodies to cell therapies, such as CAR-T, find increased application in therapy this breakthrough technology can be an important and flexible value-adding solution to enhance the yield and quality of biotherapeutics while reducing manufacturing costs.
“XMA is a game-changing technology,” noted Paul v. Kirchbach, an Xheme Advisory Board member and an international expert on sustainable polymers. “The impact of this discovery on the biotech industry will be revolutionary. Xheme is currently discussing with business partners and various biotech companies about testing XMA in bioprocessing products.”
“XMAs adaptability opens up exciting possibilities for optimizing processes and achieving better outcomes in various fields,” concluded Rashba-Step.