Recent technological advances have seen dramatic breakthroughs in the burgeoning field of immunotherapy for treatment of cancer. Of the immunotherapy approaches, chimeric antigen receptor T cells (CAR-T) in particular have shown remarkable responses in cancer patients with hematological malignancies. However, concerns remain regarding the safety profile of CAR-T cell therapies. Furthermore, CAR-T cell therapies have faced a number of challenges in the treatment of solid tumors due to challenges posed by antigen heterogeneity, the tumor microenvironment and limited persistence of CAR-T cells. Current approaches to CAR-T manufacturing rely on viral vectors for gene transfer resulting in high costs and long wait times for administration of therapy. We are developing next generation multigenic CAR-T therapies, UltraCAR-T®, for the treatment of hematological and solid tumors utilizing proprietary non-viral gene delivery and control switch technologies with the goal of achieving improved efficacy and a better safety profile. In addition, we are developing off-the-shelf immunotherapies utilizing our AdenoVerse™ platform and multifunctional therapeutics for the treatment of various solid tumors.
Treatment of autoimmune disorders usually relies on the suppression of immune response using immune-modulators or immune-suppressor drugs. Administration of these drugs may lead to severe side effects like infections and malignancy due to the attenuation of the immune system of patients. Our approach to the treatment of severe autoimmune disorders relies on local suppression of the immune system via multigenic therapies using proprietary technologies. We believe that our approach will reduce side effects while improving outcomes for patients over the long term.
Precigen is developing a portfolio of gene therapies for infectious diseases that are difficult to treat using conventional drugs. We are leveraging our expertise in bioinformatics and precision immunology to develop vaccines utilizing our AdenoVerse™ platform for treatment of various infectious diseases. In addition, we are evaluating immunotherapies based on adoptive T cell transfer for infectious disease indications.
Precigen’s UltraCAR-T therapeutic platform has the potential to disrupt the CAR-T treatment landscape by increasing patient access through shortening manufacturing time from weeks to days, decreasing manufacturing-related costs, and improving outcomes using advanced approaches for precise tumor targeting and control of the immune system. The platform brings several key advancements:
- Non-viral, multigenic vectors designed for optimal expression of various genes using our UltraVector®platform lead to better precision and control of tumor targeting and eliminates the need for virus;
- Sustained persistence and desired memory like phenotype of UltraCAR-T cells due to co-expression of mbIL15 helps address T-cell exhaustion, a common issue with current CAR-T therapies;
- T-cell control by incorporation of kill switch technology to potentially improve the safety profile;
- Rapid next-day manufacturing of UltraCAR-T cells using our proprietary non-viral gene transfer process, eliminates the need for ex vivo propagation, thus dramatically reducing wait times for patients from weeks to one day after gene transfer.
The UltraVector® platform incorporates advanced DNA construction technologies and computational models to design and assemble genetic components into complex gene expression programs. UltraVector enabled matrices facilitate rapid identification of components that yield desired gene expression. Our library of characterized genetic components and associated functional characterization data enable construction of gene programs for optimized expression of multiple effector genes using viral and non-viral delivery methods for precision medicine.
Precigen’s suite of technologies to control gene expression include RheoSwitch®, tissue specific promoters and kill switches.
RheoSwitch® gene expression platform
The RheoSwitch Therapeutic System® (RTS®) is the most clinically advanced gene switch, which allows for control and modulation of gene expression via an orally administered activator ligand with a broad dynamic range. RTS® provides patient-specific and tunable therapeutic effect with the ability to modulate the level of expression based on dosing of the activator and repeatedly turn on and off gene expression for an improved safety profile.
Tissue specific promoters
Tissue specific promoters allow for expression of a target gene only in tissue or cell type of interest for improved therapeutic effect of gene therapies.
Precigen has developed a number of kill switches to allow for targeted elimination of cell products for improved safety profile of cell therapies.
Precigen’s non-viral gene delivery platform includes the Sleeping Beauty (SB) system and AttSite™ recombinases. The SB system is the most clinically advanced transposon/transposase system that enables high-level stable gene transfer and sustained expression of transgenes in many primary cell types. The SB system relies on transposon plasmid vectors and trans-acting transposase for stable integration of transposons into the host cell genome. AttSite™ recombinases permit targeted gene delivery at a specific location in the cell genome. The AttSite™ platform opens the door to functional genomics including the development of high-expressing production cell lines for therapeutic proteins, speed and reliability of transgenic cell generation, and improvements to gene therapy safety profiles. Our non-viral platforms provide an appealing alternative to viral vectors for cell therapies by improving safety and reducing costs.
Our AdenoVerse™ technology platform includes a broad array of proprietary adenoviral vectors for efficient gene delivery for therapeutics and vaccines as well as demonstrated scale-up and production methodologies and proprietary manufacturing cell lines. AdenoVerse™ technology allows us to deliver large genetic payloads and provides ability for repeated administration.
Our multifunctional therapeutics simultaneously target multiple disease pathways that address the complexity of diseases.