AVATAR’s proprietary metabolic reprogramming technology delivers the most potent and persistent cells that are primed for clinical success.
AVATAR TECHNOLOGY
The Most Potent and Persistent Cell Therapies
-
Proprietary incubation technology mimics in-vivo tumor microenvironments, replicating key stressors like hypoxia and pressure
-
Optimized manufacturing conditions for CAR T, TIL, TCR T and Treg cells
Enhanced Cell Fitness, Even for Solid Tumors
-
AVATAR-trained cells retain metabolic fitness and are better suited for tumor microenvironments
Seamless Transfer from Discovery to Manufacturing
Designed specifically to maintain & expand primary human cells
Same in vivo environment across the instrument family
Process Development
AVATAR Odyssey
-
Identify optimal culture conditions in small scale, low cost workflows
-
Fine-tune oxygen and hyperbaric pressure levels to seamlessly translate to manufacturing scale
-
Rapidly screen cell therapy variables under physiologically relevant TME conditions to accelerate process development
Optimization
AVATAR AI
-
Real time, label free cell killing analysis designed to measure therapeutic performance within the immunosuppressive TME
-
Utilize advanced machine learning algorithms to predict the efficacy of immunotherapies and cell therapies
-
Develop rapid and accurate potency assays in physiologically relevant environments
Manufacturing
AVATAR Foundry
-
Built to effortlessly scale your process from lab to clinic
-
Enable rapid, low-cost manufacturing in a closed, automated bioreactor—ready for centralized or decentralized operations
-
Adaptable to a range of volumes, supporting both short and long manufacturing workflows
Tackling the Barriers to
Effective Cell Therapy
Cell Fitness in the Tumor Microenvironment
-
Hypoxia, high interstitial pressure, and immunosuppressive proteins create a hostile microenvironment pH for therapeutic cells
-
Conventional incubation systems fail to prepare cells for this reality—resulting in early exhaustion, poor in vivo performance, and limited clinical success
-
Cell therapies produced in small-scale quantities face the problem of emulating those conditions in separate GMP manufacturing systems
AVATAR-Expanded CAR T cells are 70% More potent in TME Conditions
Poor cytotoxicity is observed when cells are not conditioned to the challenging environment (gray bars). Cells grown under more physiological conditions (black bars) show increased potency under TME conditions.
Proven Performance Under Pressure
Explore how AVATAR technology enhances T cell potency, persistence, and efficiency by recreating the tumor micro-
environment in manufacturing.
Double the Killing Power of CAR T cells
Hyperbaric pressure and precise oxygen regulation provide optimal manufacturing conditions for producing potent & persistent therapeutic cells. The data demonstrate a significant boost to CAR T cell potency.
Conventional
CAR T cells
AVATAR
CAR T cells
Persistent Killing Over Repeated Tumor Challenges
CAR T cells manufactured under reduced oxygen and enhanced pressure exhibit persistent cytotoxic activity over repeated tumor challenges without exhaustion.
Conventional CAR T cells
AVATAR CAR T cells
Challenge 1
Challenge 2
Challenge 3
Challenge 4
Challenge 5
2X Enhanced Metabolism to Power T cell Potency
GLUT1, the primary glucose transporter in T cells, is associated with improved potency in solid tumor microenvironments and is significantly upregulated in CAR T cells expanded with AVATAR technology.
Conventional
CAR T cells
AVATAR
CAR T cells
2X Increased Rapid Cell Expansion for Clinical-Scale
Growing cells under an optimized environment increases the expansion of challenging patient-derived cells, as shown by the increased CAR T cell expansion. In this setting, ambient oxygen concentrations are maintained while hyperbaric pressure is increased.
Conventional
CAR T cells
AVATAR
CAR T cells
30% Increased Transduction and Lower Vector Cost
Viral transduction under pressurized culture conditions increases efficiency, lowering vector cost and enhancing potency. The data demonstrates how the AVATAR platform can optimize CAR T transduction efficiency.
Conventional
CAR T cells
AVATAR
CAR T cells
Sustained Tumor Killing, Even at Low E:T Ratios
TCR T cells expanded with AVATAR technology maintain strong cytotoxic function at low effector-to-target ratios that mirror the tumor microenvironment where limiting numbers of T cells must persistently kill tumor cells without exhaustion.
Effector : Target Ratio
Conventional TCR T cells
AVATAR TCR T cells
HOW IT
WORKS
AVATAR systems activate mechano- and oxygen-sensing pathways that improve:
-
Glucose uptake and oxidative metabolism
-
Stress resistance in hypoxic conditions
-
Transduction vector access during pressurization
Cells become “TME-conditioned” and carry those traits into in vivo settings. The result? Cell therapy products that are better equipped to overcome immune suppression, persist longer, and deliver superior therapeutic outcomes compared to cells expanded under traditional conditions.
Application Spotlight
Modulating Environmental Conditions to Enhance Production of Potent Cell Therapies for the Solid Tumor Microenvironment Cell therapy, such as Chimeric Antigen Receptor (CAR)-T cell therapy, has revolutionized the treatment of hematological malignancies, with high response rates that have led to five FDA approvals. In contrast, cell therapy in solid tumors remains a significant challenge for the field with relatively low efficacy and no approved therapies to date. This is due, in part, to immunosuppressive mechanisms in the tumor microenvironment (TME), which include reduced oxygen tension, high interstitial pressure, and an abundance of immunosuppressive proteins. Our work strives to modulate cell culture conditions during T cell activation, transduction, and expansion in order to manufacture the highest number of T cells exhibiting improved fitness in this harsh environment. The AVATAR technology provides discrete control of oxygen tension and hyperbaric pressure to drive metabolic and mechanoresponsive signaling. We have implemented the AVATAR technology in multiple instruments across the cell therapy development process, from preclinical to GMP, to enable users to develop and manufacture cell therapies that can overcome the suppressive TME. We will showcase data (hyperlink to download the poster) that highlights how AVATAR technology can enhance the transduction efficiency and expansion rate of CD19 CAR T cells, as compared to culture in a traditional incubator. We will expand these results to showcase enhanced cell expansion and decreased exhaustion of both healthy donor-derived bone marrow infiltrating lymphocytes and multiple myeloma patient-derived tumor infiltrating lymphocytes, as a result of culture in the low oxygen, high pressure AVATAR system. These studies highlight the integral role that cell culture conditions play in the efficient expansion of therapeutic cell therapies while maintaining phenotypes associated with efficacious and durable anti-tumor effects. Check out the poster here: https://www.xcellbio.com/isct-2024-poster.