Pioneering the Next Generation of Immunotherapy
Our platform targets tumors with precision, enabling patients to live longer, healthier lives.
Many Patients Don’t Respond to Current Immunotherapies
Although 90% of all cancers manifest as solid tumors, conventional chimeric antigen receptor (CAR) T-cell immunotherapies are effective in only a small number of hematologic cancers and melanoma, leaving limited treatment options for patients with solid tumor cancers. Due to the tumor’s hostile microenvironment, immune cells produced by current CAR T-cell treatments are disabled by the tumor’s own protective mechanisms. Furthermore, the diversity of cells in solid cancers enables some to escape immune targeting, resulting in metastasis to other parts of the body.
In patients whose cancers are responsive to conventional CAR T-cell immunotherapies, the current standard of care has significant limitations. Not only does overstimulating the immune system carry the risk of treatment-limiting adverse events, but the ex vivo manufacturing process requires patients to wait up to 6 weeks to receive the first dose of personalized immunotherapy, losing critical time in the fight against metastasis. Meanwhile, CAR T cells often lose some of their cancer-fighting activity due to the days-long process that is needed to grow the appropriate therapeutic dose. Additionally, patients must undergo lymphodepletion via chemotherapy prior to treatment, putting them at risk for dangerous infections.
Aside from the emotional and physical toll on patients, the time and expense of generating T cells ex vivo has pushed CAR T-cell immunotherapies even further out of reach. The limited scalability and other logistical challenges of this approach mean that patient demand often exceeds capabilities, highlighting the need for more accessible, scalable, and effective treatments for solid tumor and blood cancers.
Umoja’s solution: “off the shelf” cell therapies
Umoja is pioneering complementary solutions to the next generation of cell therapies: in vivo CAR T-cell therapeutics, and RACR-induced cytotoxic lymphocytes (iCIL).
Umoja’s integrated approach overcomes many of the limitations of current generation ex vivo cellular immunotherapies. Our platforms —VivoVec™, iCIL™, RACR/CAR™, and TumorTag™,— work in tandem to generate and support an army of cancer fighting T cells that target tumors and their stromal cells, potentially reducing adverse events and prolonging remissions for patients.
* RACR – rapamycin activated cytokine receptor
VivoVec: In Vivo Gene Delivery
Manufactured in house, our VivoVec gene delivery product uses proprietary, third-generation lentiviral vector technology with a 20-year established safety record. When introduced to the patient, VivoVec enables the body to make its own cancer-fighting CAR T cells that are genetically retooled with our RACR/CAR systems to allow clinicians to control their function. This off-the-shelf technology eliminates the complexity, delay, and expense of externally manufactured cell therapies while offering ex vivo applicability in settings in which a traditional CAR T-cell therapeutic approach is more appropriate.
RACR-induced cytotoxic lymphocytes (iCIL)
Umoja’s innovative RACR-induced cytotoxic lymphocyte platform leverages our RACR technology in a novel cell manufacturing process to generate synthetic cancer fighting cells from induced pluripotent stem cells at massive scale. These cells, termed induced cytotoxic innate lymphocytes or iCILs, can be administered to patients to augment their endogenous anti-tumor immune function, and to work together with VivoVec-generated in vivo CAR T-cells. Similar to VivoVec-generated CAR T-cells, iCILs leverage our RACR/CAR™ and TumorTag™ platforms respectively to support cell survival and target tumors and their stromal cells, potentially reducing adverse events and prolonging remissions for patients.
RACR/CAR: In Vivo Cell Programming
Our Rapamycin-Activated Cytokine Receptor (RACR) payload architecture uses an approved small-molecule drug (rapamycin) with a long-term safety profile to eliminate the need for lymphodepletion via chemotherapy. By providing a survival and expansion signal directly to engineered immune cells and rendering transduced T cells resistant to the native antiproliferative activity of rapamycin, the RACR system supports the survival and expansion of CAR T cells generated inside the body via VivoVec-mediated gene delivery.
The RACR system is designed to leverage the native antiproliferative pharmacologic activity of rapamycin to facilitate in vivo gene delivery via the VivoVec platform. At the same time that rapamycin is activating and enhancing the activity of VivoVec transduced cells via the RACR system, it inhibits tumor growth, suppresses immune responses against VivoVec particles, enabling the readministration of VivoVec-transduced drug products and suppresses rejection responses against the transgenes expressed in VivoVec-transduced cells. These secondary mechanisms of action of rapamycin are part of the core design principles of the RACR system and are essential to maximizing the potency of RACR-expressing products and enabling the long-term expansion and survival of CAR T cells generated in vivo.
TumorTag: Universal CAR Tumor Targeting
This small molecule binds to cancer and its stromal cells, “tagging” them as targets for CAR T cells. This results in a precise, potent attack on the cancer as well as a combinatorial targeting of cancer cells and stromal elements that tumors use to evade the body’s defenses. TumorTag is applicable to an array of cancer therapies and can be leveraged to use a universal CAR with ex vivo–manufactured cells (autologous or allogeneic) to increase targeting flexibility.
A Powerful Therapeutic Approach
These core platforms work together in a complementary way. First, we apply VivoVec and the RACR/CAR payload architecture to stimulate the body to grow tumor-fighting T cells. We then deploy TumorTags to direct these tumor-fighting T cells to attack the tumor. The precision and control afforded by the integrated mechanisms of action of the platforms maximize the potential therapeutic effect while minimizing the risk of adverse events in the patient.