On April 17, 2018 Torque, an immuno-oncology company developing Deep Primed cellular therapies with pharmacologic control to direct immune power deep within the tumor microenvironment, reported preclinical data for the company’s Deep-Primed IL-15 and Deep-Primed IL-12 programs demonstrating their activity compared to systemically administered IL-15 and IL-12 (Press release, Torque Therapeutics, APR 17, 2018, View Source [SID1234525537]). These data were presented at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago.
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Torque is developing a new class of Deep-Primed immune cell therapeutics to dramatically expand cell therapy cures for cancer. Deep-Priming uses advanced material engineering to anchor immune-stimulatory drugs directly to the surface of multi-targeted, antigen-primed T cells to activate both the adaptive and innate immune system with pharmacologic control in the tumor microenvironment. This approach does not require genetic engineering and enables tunable loading of precise doses of cytokines onto the surface of T cells to deliver sustained and controlled immune activation.
"Both Il-15 and IL-12 are potent cytokines capable of inducing strong anti-tumor immune responses, yet their clinical use as systemic therapies is limited by the potential for severe toxicities," said Thomas Andresen, PhD, Chief Scientific Officer of Torque. "Anchoring these powerful immune activators to the surface of T cells that traffic to tumors is a unique approach to direct immune power in the tumor microenvironment. These preclinical studies demonstrate superior efficacy for this approach compared to systemic administration of these same cytokines and are the foundation for the first clinical trials that will begin later this year for Deep IL-15."
Highlights of the three preclinical presentations follow, and copies of the posters are available for download on the Torque website: https://bit.ly/2FZtPOW
Abstract 3575 / Poster 13: "Cell therapy with surface-tethered IL-12 provides immune system priming and strong anti-tumor activity"
Presenter: Jon Nardozzi, PhD, Torque; Session: Adoptive Cell Therapy 3
Key findings from the study:
Deep IL-12 Priming technology enables high loading of IL-12 doses on the surface of tumor-specific T cells.
Deep IL-12 Priming substantially increases tumor killing survival with adoptively transferred tumor-specific T cells in an aggressive solid tumor model and is superior to systemically administered IL-12.
Administration of repeat doses of Deep IL-12 Primed T cells without pre-conditioning (lymphodepletion) further increases tumor killing and survival with adoptively transferred T cells in this aggressive solid tumor model.
Deep IL-12 Primed T cells activate an endogenous immune response but do not induce overt toxicities such as weight loss or sustained systemic cytokine release.
Abstract 3577 / Poster 15: "Deep IL-15 provides autocrine stimulation and expansion of autologous T cells driven by controlled concentrated release of IL-15"
Presenter: Pengpeng Cao, PhD, Torque; Session: Adoptive Cell Therapy 3
Key findings from the study:
Deep IL-15 Priming technology loads IL-15 on T cells with a highly controlled dose per cell and provides slow release of IL-15 for autocrine stimulation and sustained adoptive T cell therapy expansion.
In contrast to systemically delivered IL-15, Deep IL-15 substantially increases target CD8 T cell concentration in the tumor, without significant systemic IFNg levels or endogenous CD8 and NK cell expansion, due to lack of systemic exposure.
Torque’s fully closed manufacturing process that uses a proprietary dendritic cell priming process generates several billion, antigen-primed human T cells with an average of 20% reactivity and >95% T cell purity (demonstrated with autologous cells from healthy human donors).
Clinical trials using this manufacturing process for Deep IL-15 Primed multi-target T cells are expected to initiate in 2018.
Also at AACR (Free AACR Whitepaper), the Irvine Lab of the Koch Institute at MIT presented data on IL-12 and IL-15 formulated in nanogels and anchored to T cells using technology developed in the Irvine Lab. Torque has built upon the Irvine Lab’s work to create the Deep-Priming technology platform. The Irvine Lab is directed by Darrell Irvine, PhD, who is a co-founder of Torque and Chairman of Torque’s Scientific Advisory Board, Professor at the Massachusetts Institute of Technology, and an Investigator of the Howard Hughes Medical Institute.
Abstract 3565 / Poster 3: "T cell receptor signaling-responsive single chain IL-12 and IL-15 superagonist nanogel ‘backpacks’ to enhance adoptive cell therapy in solid tumors"
Presenter: Michael Fichter, PhD, Koch Institute for Integrative Research at MIT; Session: Adoptive Cell Therapy 3
Key findings from the study:
IL-15 nanogels anchored to tumor-targeted T cells induces significant and specific expansion of the adoptively transferred T cells in tumors and lymph nodes that is superior to systemic IL-15.
IL-15 nanogels anchored to T cells substantively improved the efficacy of an adoptive T cell therapy against solid tumors while reducing cytokine-induced side effects triggered by systemically administered IL-15.
In a separate experiment, IL-12 nanogels anchored to CD8 effector cells induced substantial cell activation.
About Deep-Primed Immune Cell Therapeutics
Torque’s Deep-Priming platform is based on 10 years of research and development to combine very potent immunomodulatory drugs with T cells to drive a powerful immune response with pharmacologic control in the tumor microenvironment. We are developing Deep-Primed T cells using a focused set of immunomodulators—initially IL-15, IL-12, and TLR agonists—that activate both innate and adaptive immunity. Administering these immunomodulators systemically to a patient can cause lethal toxicity by activating immune cells throughout the body. Deep-Primed therapeutics are designed to activate T cells and focus the immune response to target the tumor, without systemic exposure. This is achieved by:
Anchoring the immunomodulators to the surface of T cells to activate and direct the immune response in the tumor microenvironment
Modular antigen priming of T cells to target multiple, tumor-associated antigens using a proprietary cell-processing technology
In hematologic cancers, this new class of immune therapeutics has the potential to improve on the initial success of single-target CAR-T therapeutics. For solid tumors, Deep-Primed T-cells have the potential to enable efficacy against tumors with heterogeneous antigens protected by hostile microenvironments, which are not readily addressable with the first generation of immune cell therapies.