ALLOGENEIC CAR T —
THE NEXT REVOLUTION IN CELL THERAPY
Allogene is working to overcome the limitations of autologous CAR T therapies by creating investigational allogeneic CAR T cell products, or AlloCAR T™ products. Unlike autologous cell therapy, AlloCAR T™ products use T cells from healthy donors.
These cells are isolated in a manufacturing facility, engineered to express CARs to recognize and destroy cancer cells, and modified via gene editing to limit autoimmune response when given to a patient. These products are then stored for off-the-shelf use on demand. We believe that, at scale, a single manufacturing run has the potential to yield treatment for 100+ patients.
WHY ALLOGENEIC CELL PRODUCTS
HAVE THE POTENTIAL TO LEAD THE REVOLUTION
- Potential to treat all eligible patients
- Repeat dosing, if needed
- No need for complex logistics
- Scalable and efficient manufacturing
- Potential to treat 100+ patients from a single manufacturing run
- Lower ancillary costs
- Off-the-shelf for on-demand treatment
- Less product variability, made from healthy T cells
- Multiplex gene-engineering and gene-editing capabilities
- Opportunity for product optimization
THE DIFFERENCE STARTS WITH HEALTHY DONORS
APPLYING INNOVATIVE TECHNOLOGY TO
The process for manufacturing our investigational off-the-shelf AlloCAR TTM products begins by harvesting healthy, selected, screened and tested T cells from healthy donors. The benefit of starting with healthy donors is that a larger portion of eligible patients, including those who are critically ill and lack a robust supply of T cells for harvest and expansion, can potentially receive treatment.
Additionally, with our platform no patient needs to undergo leukapheresis (a laboratory procedure in which a patient’s white blood cells are separated and the remaining blood cells and plasma are returned to the patient).
Next, the T cells are engineered to express CARs, which recognize certain cell-surface proteins that are expressed in hematologic or solid tumors. For example, ALLO-501A, one of our investigational products, recognize CD19, a cell-surface protein expressed on B-cells, including cancerous B-cells; it is just the first in a line of AlloCAR TTM products we plan to develop. The next step in the process involves gene editing to reduce the risk of graft-vs-host disease (GVHD) and allogeneic rejection. A T cell receptor gene is knocked out to avoid GVHD. The CD52 gene is knocked out to render the CAR T product resistant to anti-CD52 antibody treatment. ALLO-647, our proprietary investigational anti-CD52 monoclonal antibody, is designed to suppress the host immune system and allow the AlloCAR TTM product to stay engrafted in order to achieve full therapeutic impact.
The engineered T cells then undergo a purification step and are ultimately cryopreserved in vials for delivery to patients.
*In collaboration with Notch Therapeutics.
EXPANDING TARGET REPERTOIRE
- Target selection / validation
- CAR optimization
- Multitargeting CARs
iPSCs: THE ROAD TO A RENEWABLE CELL SOURCE
TurboCAR™: TURBOCHARGING CAR T CELLS
- TurboCAR™ is designed to recapitulate cytokine signaling selectively in CAR T
– Does not stimulate host immune cells which could cause systemic toxicity or reject CAR
– Delivers survival benefit selectively to CAR T cells
- Opportunities for development include
– Improving the efficacy of CAR T cells
– Reducing CAR T cell dose requirement
– Overcoming exhaustion to enable CAR T to be used for solid tumors
- Improved engraftment and persistence and delayed exhaustion seen preclinical studies
ELIMINATION OF TCR IN DONOR T CELLS MAY CONTROL GvHD
ALLO-647: SELECTIVE LYMPHODEPLETION MAY DELAY GRAFT REJECTION
Host T Cell Recovery Delayed by Addition of Anti-CD52
STATE-OF-THE-ART, IN-HOUSE MANUFACTURING FOR ON-DEMAND AlloCAR T™ AVAILABILITY
Maintaining state-of-the-art, world-class manufacturing capabilities is at the core of our strategy to deliver readily available cell products faster, more reliably, and at greater scale. Our manufacturing facility, Cell Forge 1, located in Newark, California, in the eastern region of the San Francisco Bay Area, is designed for clinical and commercial manufacturing, analytical testing and distribution of cell products. This facility provides in-house quality assurance and quality control, per current good manufacturing practices (cGMPs), to ensure a reliable supply of AlloCARs™ for our clinical programs and commercial products, pending regulatory approval.
MODULAR, FLEXIBLE DESIGN
Our modular, 136,000 square-foot facility was designed for growth. It currently has three production suites, with the ability to accommodate five as we look ahead to bringing new therapies onto the market.
IN-HOUSE QUALITY CONTROL AND TESTING
We believe in the critical importance of understanding the quality of our investigational AlloCAR T™ products, which is why we operate the entire scope of product testing and maintain an open data strategy in-house.
COMMITMENT TO SUSTAINABILITY
Cell Forge 1 is a carbon-free facility that is fully powered by electricity, much of which will be delivered by the 2,400 solar panels on the rooftop.
We are awaiting LEED Gold certification for both facility design and operation.
We included large windows throughout the facility to promote a culture of transparency and connection. Open workspaces, as well as the facility’s proximity to Allogene’s Headquarters, allow for regular cross-functional collaboration.
LEARN MORE ABOUT ALLOGENE'S MANUFACTURING CAPABILITIES
Some AlloCAR T™ products for Allogene's clinical trials are currently manufactured in a dedicated, purpose-built GMP suite by a contract manufacturing organization (CMO), which is expected to remain a component of our manufacturing strategy.