On November 8, 2019 Torque, a clinical-stage immuno-oncology company developing Deep Primed T cell immunotherapy to direct immune power deep within the tumor microenvironment, reported new preclinical data for its lead Deep IL-15 Primed T cell, Deep Il-12 Primed T cell, and Deep TLR Primed T cell therapeutics programs as well as for the company’s proprietary Slipstream process for manufacturing these first-in-class, multi-targeted cellular immunotherapies (Press release, Torque Therapeutics, NOV 8, 2019, View Source [SID1234550775]). The data are being presented today at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 34th Annual Meeting being held November 6–10, 2019 in National Harbor, Maryland.
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"These studies build on previous findings demonstrating the potential for the Deep-Primed technology platform to create a new class of multi-targeted T cell therapy that targets tumor antigens with specificity in the tumor microenvironment, with integrated and coordinated cytokine activation that drives a full response against tumors with heterogenous antigens," said Thomas Andresen, PhD, Chief Scientific Officer of Torque. "These preclinical studies provide the foundation for Torque’s first clinical trial for Deep IL-15 Primed multi-targeted T cells that is now under way, and for the Deep IL-12 and Deep TLR programs that we are preparing to move into clinical trials in the latter part of this year and in 2020, including a combination study of Deep IL-12 and Deep IL-15 Primed T cells."
Highlights of the four preclinical presentations follow, and copies of the posters are available on the Torque website: https://bit.ly/34yZnTU
Poster #P671: "Delivery of TLR7 agonists by Deep-Primed T cells induces immune activation and improves anti-tumor activity in mice while circumventing systemic toxicity"
Presenter: Austin Boesch, PhD, Torque
Key findings from the study:
In preclinical models, Deep TLR-Primed T cells display superior efficacy, pharmacodynamics, and safety compared to T cells alone or to T cells co-administered with systemic TLR agonists.
Torque’s Deep-Primed technology allows the delivery of small molecules to the tumor microenvironment, with controlled doses.
Compared to intratumoral delivery, agonist delivery via Deep-Primed tumor antigen-specific autologous T cells can target a wider variety of tumors, including distant metastases.
Deep TLR-Primed T cells have the potential to improve agonist pharmacokinetic profile through sustained delivery over time in the tumor microenvironment and draining lymph nodes, with limited systemic exposure.
Poster #P211: "Combining Deep IL-12 Primed and Deep IL-15 Primed T cells leverages complementary mechanisms to enhance anti-tumor activity"
Presenter: Katharine Sackton, PhD, Torque
Key findings from the study:
In preclinical models, modular tethering of Deep IL-12 and Deep IL-15 to T cells uniquely leverages their complementary functions as immunomodulators to maximize anti-tumor activity, without notable toxicity.
Poster #P473: "Adoptive Transfer of Deep IL-12 Primed T-cells Increases Sensitivity to PD-L1 Blockade for Superior Efficacy in Checkpoint Refractory Tumors"
Presenter: Gulzar Ahmad, PhD, Torque
Key findings from the study:
In a preclinical checkpoint-refractory cancer model, adoptive cell transfer with tumor-specific T cells carrying surface-tethered Deep IL-12, which focuses immune activity in the tumor microenvironment, repolarizes immunosuppressive cells in the tumor, enhances anti-tumor efficacy, and synergizes with checkpoint inhibition.
Poster #P157: "Optimized process for manufacturing Deep-Primed T cells creates product with improved functional characteristics and reactivity against multiple tumor-associated antigens"
Presenter: Shawn P. Carey, PhD, Torque
Key findings from the study:
Torque’s Slipstream cell manufacturing process is optimized to produce Deep-Primed multi-targeted T cells with substantive increases in characteristics associated with clinical efficacy: Antigen reactivity, memory phenotype, and polyfunctionality.
Modularity of the Slipstream process has been demonstrated by simultaneously training T cell clones reactive to cancer and virus-associated antigens.
Deep-Primed multi-targeted T cells with cell-associated Deep IL-15 or Deep IL-12 drives enhanced T cell function in vitro.
About Deep-Primed T Cell Therapeutics
Torque is developing a new class of Deep-Primed cellular immunotherapy designed to overcome the key challenges limiting broad use of cellular therapy in oncology, including the ability to target tumors that express multiple heterogeneous antigens, the ability to overcome the immunosuppressive tumor microenvironment that shuts down T cell function, and the need for cost-effective outpatient treatment with a high margin of safety. Deep-Priming is a unique technology platform that harnesses natural T cell biology and the power of cytokine activation to prime and boost a full immune response in the tumor microenvironment. Deep-Primed T cells are designed to:
Activate a Deep Immune Response Against Solid Tumors & Hematologic Cancers: Natural T cell receptors are primed to target multiple tumor antigens and retain their natural ability to integrate with the full immune system to direct a deep and comprehensive immune response against cancer.
Prime and Boost Broad Immune Cell Engagement to Overcome Immunosuppression in the Tumor Microenvironment: Deep-Primed T cells carry surface-anchored cytokines and immunomodulators to jump-start the engagement and coordination of the full network of immune cells to direct immune power in the tumor microenvironment, without significant systemic exposure.
Torque’s first clinical program, TRQ-1501 (Deep IL-15 Primed T cells), has received FDA Fast Track designation for the treatment of relapsed or refractory solid tumors and lymphomas and is currently in a Phase 1/2 clinical trial for this indication.