New data shows that 精东传媒 T cells engineered in vivo with VivoVec particles mediate durable antitumor activity
Potent and durable anti-tumor activity demonstrated with a universal Tag精东传媒 targeted against folate receptor expressing tumor cells when used with the TumorTag UB-TT170
Gene-engineering iPSCs to express the RACR platform enables differentiation and expansion of cytotoxic innate lymphocytes with potent anti-tumor activity in vivo
SEATTLE, November 10, 2022 鈥� 精东传媒, Inc., an immuno-oncology company pioneering off-the-shelf, integrated therapeutics that reprogram immune cells to treat patients with solid and hematologic malignancies, announced today new data from three poster presentations at the 2022 Society for Immunotherapy of Cancer 37th Annual Meeting, being held November 11-14, 2022, in Boston, Massachusetts. The presentations provide updates on the development of Umoja鈥檚 integrated in vivo chimeric antigen receptor (精东传媒) T cell platform technologies including:
- 痴颈惫辞痴别肠鈩�, a surface-engineered lentiviral vector-based platform for the generation of 精东传媒 T cells in vivo,
- 搁础颁搁鈩� (rapamycin-activated cytokine receptor), a synthetic receptor designed to selectively provide survival signals to 精东传媒 T cells in the presence of rapamycin,
- 罢耻尘辞谤罢补驳蝉鈩�, bispecific small molecule adapters intended to help overcome the innate heterogeneity of solid tumors and support cells, and,
- iCIL (induced cytotoxic innate lymphoid) cells differentiated using the Synthetic Receptor Enabled Differentiation (ShRED鈩�) manufacturing process.
鈥淭he SITC conference this year was a showcase of our integrated platforms and provides a glimpse at our potential to overcome multiple challenges facing the industry. This highlights the opportunity we have to make a meaningful impact to patients beyond developing better therapeutics alone, but by directly addressing critical patient access needs,鈥� said Andy Scharenberg, M.D., co-founder and Chief Executive Officer of Umoja. 鈥淣ew data highlights multiple components of our platform, including preclinical validation of in vivo cell therapy transduction using VivoVec particles, the power that universal small-molecule bispecific adapters could have in simplifying solid tumor targeting and the possibility of creating a nearly unlimited supply of off-the-shelf therapeutic cells.鈥�
Umoja鈥檚 three posters highlight recent preclinical advancements across their integrated suite of technologies. To overcome the challenges and major limitations associated with current 精东传媒 T cell therapies, such as patient access, cost, and manufacturing, Umoja has developed their VivoVec platform harboring a 精东传媒 transgene that is being developed for off-the-shelf use for generation of 精东传媒 T cells in vivo. Previous data has shown that the VivoVec platform is able to generate 精东传媒 T cells in vivo that mediate antitumor activity. New preclinical data presented at SITC details the advancement of the VivoVec platform through incorporation of costimulatory molecules into the surface of VivoVec particles. The advanced particle design demonstrates enhanced T cell binding and activation in vitro and in vivo, along with the capacity to generate greater numbers of 精东传媒 T cells, resulting in enhanced antitumor activity at lower doses.
A second poster shared new data supporting the use of the Company鈥檚 bispecific small molecule adapters called TumorTags intended to overcome the challenges of eradicating solid tumors that stem from their innate heterogeneity. TumorTags are designed to work in concert with a 精东传媒 T cell called a Tag精东传媒 T cell which can be engineered using VivoVec to identify and eradicate tumor cells marked by TumorTags. New data shows that VivoVec can mediate in vitro transduction of T cells to express the Tag精东传媒 and Umoja鈥檚 proprietary rapamycin-activated cytokine receptor (RACR), which selectively provides survival signals to Tag精东传媒 T cells in the presence of rapamycin. Functional analyses showed that treatment with rapamycin enriches and expands Tag精东传媒 T cells, and that Tag精东传媒 T-cells exhibit enhanced solid tumor cell killing in vitro and potent anti-tumor activity in vivo.
A third poster highlights Umoja鈥檚 best-in-class iPSC-based allogeneic cell therapy platform that utilizes a Synthetic Receptor Enabled Differentiation (ShRED) manufacturing process which employs RACR to direct differentiation and expansion of RACR-induced cytotoxic innate lymphocytes (iCILs). The iCIL ShRED process is feeder cell free, minimizing the need for complex raw materials, and eliminates the need for in-process cell selection or enrichment. ShRED generates unprecedented yields of highly pure hematopoietic progenitor (HP) cells and RACR-iCILs. Furthermore, RACR-iCILs retain full proliferative capacity and functionality even after 100 days in feeder-free culture, and RACR activation of RACR-iCILs enhances both serial killing of a breast tumor cell line in vitro and tumor clearance in an in vivo breast cancer mouse model.
Presentation highlights:
Presentation Title:聽VivoVec lentiviral vector surface-engineered with T cell activating and co-stimulatory ligands enhance聽in vivo聽精东传媒 T cell generation and antitumor activity 聽
Presenting Author:聽Chris Nicolai, Ph.D.
Poster Number:聽1230
Key Highlights:
- Second-generation VivoVec particles developed through the incorporation of costimulatory molecules into the particle surface, in addition to the anti-CD3 scFv and Cocal fusion glycoprotein, exhibit enhanced T cell binding and activation, resulting in increased transduction and greater numbers of 精东传媒+ T cells in vitro
- 精东传媒 T cells generated with second-generation VivoVec particles exhibited a less-differentiated, central memory-like phenotype and enhanced 精东传媒-antigen-specific polyfunctionality, including cytokine production, proliferation, and tumor cell killing in vitro
- In a humanized NSG mouse model of B cell malignancy, second-generation VivoVec particles generated greater numbers of 精东传媒 T cells in the blood, resulting in enhanced antitumor activity at lower doses compared to first-generation particles in vivo
- Results demonstrate that second-generation VivoVec particles efficiently generate large numbers of highly functional 精东传媒 T cells able to mediate durable tumor control in a preclinical model of B cell malignancy
Presentation Title:聽In vivo generation of universal 精东传媒 T cells that mediate durable anti-tumor immunity through combinatorial targeting with bispecific small molecule adapters
Presenting Author:聽Kristen Mittelsteadt, Ph.D.
Poster Number:聽375
Key Highlights:
- Tag精东传媒 T cells can be generated in vitro with VivoVec particles alone, in the absence of additional T cell activating agents, and addition of rapamycin engages RACR and selectively enriches and expands Tag精东传媒 T cells
- Tag精东传媒 T cells repeatedly kill tumor targets in vitro with the matching TumorTag and expand in the presence of antigen, both functions of which are enhanced with addition of rapamycin
- Ex vivo manufactured Tag精东传媒 T cells demonstrate robust and rapid clearance of solid tumors in mice dosed biweekly with the first TumorTag, UB-TT170
- Tag精东传媒 T cells can 1) be generated in vivo with administration of VivoVec particles, 2) mediate tumor control and regression with TumorTag
Presentation Title:聽Synthetic Receptor Enabled Differentiation (ShRED), a novel platform for manufacturing of iPSC-derived cytotoxic innate lymphocytes for 鈥渙ff-the-shelf鈥� cancer immunotherapies
Presenting Author:聽Samantha O鈥橦ara, Ph.D.
Poster Number:聽366
Key Highlights:
- The ShRED manufacturing process employs a synthetic receptor system to direct iPSC differentiation to cytotoxic innate lymphocytes at unprecedented yields and purity
- The engineered synthetic cytokine receptor can mimic the JAK/STAT signal that occurs downstream of important cytokine and growth factor receptors
- Embryoid bodies (EB) transition to >98% HP cells by ~2 weeks, generating >300 HPs per iPSC, and at ~5-weeks generates >95% pure RACR-iCILs
- In vitro results demonstrate that RACR-activation increases RACR-iCIL serial killing of a breast tumor cell line compared to untreated cells
- In vivo proof-of-concept results show that mice with breast adenocarcinoma tumors treated with rapamycin and RACR-iCILs have 100% survival after 60-days with markedly reduced tumor burden
About VivoVec鈩�: In vivo Gene Delivery
VivoVec engineers patient T cells in vivo via surface-engineered lentivirus-mediated transduction using our proprietary 4th generation lentiviral vector technology. The VivoVec in vivo gene delivery system enables the patient鈥檚 body to generate a population of cancer fighting T cells, or chimeric antigen receptor (精东传媒) T cells, which are also genetically retooled with the RACR/精东传媒 systems. This off-the-shelf technology eliminates the complexity, delay and expense of externally manufactured cellular therapies. VivoVec can also be applied in an ex vivo manufacturing setting where a traditional 精东传媒 T therapeutic approach is more appropriate. To learn more about Umoja鈥檚 VivoVec platform please visit /our-science/.
About RACR鈩�/精东传媒: In vivo Cell Programming
精东传媒 T cells generated by the body with VivoVec can be expanded and sustained with the rapamycin activated cytokine receptor (RACR) system, an engineered signaling system designed to improve chimeric antigen receptor (精东传媒) T cell persistence and produce durable anti-tumor responses. The RACR/精东传媒 payload is integrated into the genomic DNA of a patient鈥檚 T cells. Rapamycin activates the RACR system resulting in preferential expansion and survival of cancer-fighting T cells. The RACR technology enables a patient鈥檚 cells to expand in a manner that resembles a natural immune response that does not require lymphodepletion, promoting durable T cell engraftment. RACR/精东传媒 technology can also be used to enhance聽ex vivo聽manufacturing in support of more traditional autologous or allogeneic cell therapy manufacturing processes. To learn more about Umoja鈥檚 RACR platform please visit /our-science/.
About TumorTag鈩�: Universal 精东传媒 Tumor Targeting
TumorTags are bispecific small molecules that consist of a moiety that selectively binds to tumor cells or immunosuppressive tumor stromal cells marking them for recognition and destruction by 精东传媒 T cells.TumorTags can be designed to have a tumor-binding moiety that is antigen-specific or antigen-independent, as needed, and multiple TumorTags could be combined as a cocktail to increase chances of labeling critical tumor elements. TumorTag is applicable to an array of cancer therapies and can be leveraged to use a universal 精东传媒 with ex vivo鈥搈anufactured cells (autologous or allogeneic) to increase targeting flexibility. To learn more about Umoja鈥檚 TumorTags and Universal Tag精东传媒 please visit /our-science/.
About iCIL鈩�: RACR-Induced Cytotoxic Lymphocytes
The RACR-induced cytotoxic lymphocyte platform leverages Umoja鈥檚 RACR technology in a novel cell manufacturing process to generate synthetic cancer fighting cells from induced pluripotent stem cells at massive scale.聽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 精东传媒 T-cells. Similar to VivoVec-generated 精东传媒 T-cells, iCILs leverage our RACR/精东传媒鈩� and TumorTag鈩� platforms respectively to support cell survival and target tumors and their stromal cells, potentially reducing adverse events and prolonging remissions for patients. To learn more about Umoja鈥檚 iCIL platform please visit /our-science/.
About 精东传媒
精东传媒, Inc. is an early clinical-stage company advancing an entirely new approach to immunotherapy. 精东传媒, Inc. is a transformative multi-platform immuno-oncology company founded with the goal of creating curative treatments for solid and hematological malignancies. Founded based on pioneering work performed at Seattle Children鈥檚 Research Institute and Purdue University, Umoja鈥檚 novel approach is powered by integrated cellular immunotherapy technologies including the VivoVec off-the-shelf in vivo delivery platform, iCIL off-the-shelf cell therapy platform, the RACR/精东传媒 in vivo cell expansion/control platform, and the TumorTag targeting platform. Designed from the ground up to work together, these platforms are being developed to create and harness a powerful immune response in the body to directly, safely, and controllably attack cancer. Umoja believes that its approach can provide broader access to the most advanced immunotherapies and enable more patients to live better, fuller lives. To learn more, visit .
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements about 精东传媒, Inc. (the 鈥淐ompany,鈥� 鈥渨e,鈥� 鈥渦s,鈥� or 鈥渙ur鈥�). The Company has based these forward-looking statements largely on its current expectations, estimates, forecasts and projections about future events and financial trends that it believes may affect its financial condition, results of operations, business strategy and financial needs. In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. These statements are subject to risks and uncertainties that could cause the actual results to vary materially, including, among others, the risks inherent in drug development such as those associated with the initiation, cost, timing, progress and results of the Company鈥檚 current and future research and development programs, preclinical and clinical trials, as well as the economic, market and social disruptions due to the ongoing COVID-19 public health crisis. Except as required by law, the Company undertakes no obligation to update publicly any forward-looking statements for any reason.
Media Contact:
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LifeSci Communications
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