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Immune Design demonstrates potential of "Prime-Pull" immunotherapy approach
SEATTLE and SOUTH SAN FRANCISCO, Calif.—Immune Design, a clinical-stage immunotherapy company focused on oncology, has announced new preclinical data showing that a dendritic-cell-targeting lentiviral vector from its ZVex immunotherapy platform administered with G100, which contains a potent synthetic TLR4 agonist, synergize with immune check point inhibitors and demonstrate potent local and systemic anti-tumor activity in cancer models. These data are being presented at the 30th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) Conference, National Harbor, Maryland, November 4-8, 2015.
"These findings further illustrate the potential of ZVex-based product candidates and G100 to play an important role in the emerging field of cancer immunotherapy, especially in potential combination therapies with immune checkpoint inhibitors," said Jan ter Meulen, M.D., Ph.D., chief scientific officer at Immune Design. "Mechanistically, it is generally believed that the generation of tumor-specific CD8 T cells can improve the clinical efficacy of checkpoint inhibitors, especially in patients with insufficient T cell responses. These preclinical data provide a strong rationale for our ongoing and planned clinical trials which combine LV305, CMB305 and G100, agents from our ZVex and GLAAS discovery platforms, with KEYTRUDA and Atezolizumab."
In the presentations, Immune Design scientists present data showing that in the murine B16 melanoma model, intratumoral injection of G100 improves the trafficking of ZVex-induced antigen-specific CD8 T cells into tumors and induces systemic anti-tumor immunity mediated by antigen spreading. This discovery that Immune Design's two platforms appear to "pull" T cells (G100) that were "primed" (ZVex agent) into the tumor potentially opens up new possibilities of enhancing the immunotherapy of solid tumors by changing the tumor microenvironment. In addition, combining G100 or a ZVex agent with both anti-PD1 and anti-PDL1 antibodies demonstrated increased efficacy in this experiment. The presentations are entitled "Intratumoral Injections of G100 (synthetic TLR4 agonist) Increases Trafficking of Lentiviral Vector-induced Antigen-specific CD8 T Cells to the Tumor Microenvironment" and "Checkpoint Inhibitors Synergize with Therapeutic Platforms, ZVex and GLAAS by Enhancing Lentiviral Vector-induced Tumor-specific Immunity and Adjuvant-mediated Anti-tumor Efficacy."
These abstracts will be published in the Journal for ImmunoTherapy for Cancer on November 4, 2015, and the posters will be posted on the publications page of the Immune Design website following presentation at the conference.
G100 is a product candidate generated from the company's GLAAS discovery platform, and includes a specific formulation of Glucopyranosyl Lipid A (GLA), a synthetic, toll-like receptor-4 (TLR-4) agonist. G100 is part of Immune Design's intratumoral immune activation, or 'Endogenous Antigen' approach to treating cancer, which leverages the activation of dendritic cells, T cells and other immune cells in the tumor microenvironment to potentially create a robust immune response against the tumor's preexisting diverse set of antigens. Preclinical and clinical data have demonstrated the ability of G100 to activate dendritic cells in tumors and to increase antigen-dependent systemic humoral and cellular Th1 immune responses. A Phase 1 study of G100 in patients with Merkel cell carcinoma (MCC) recently completed enrollment, and Immune Design presented data at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting. In the first eight patients in MCC study, G100 had an acceptable safety profile and the combined therapy of G100 followed by radiation and or surgery resulted in an objective response rate (ORR) of 50 percent. A second Phase 1 trial is planned to examine intratumoral administration of G100 with intravenous administration of KEYTRUDA (pembrolizumab), Merck's anti-PD-1 therapy, in patients with follicular non-Hodgkin's lymphoma receiving local radiation. In addition to an evaluation of the safety of the combination, the study will assess the response in both injected and non-injected lesions.
ZVex is Immune Design's discovery platform designed to activate and expand the immune system's natural ability to create tumor-specific cytotoxic T cells (CTLs) in vivo.
The ZVex delivery system uses a re-engineered virus to carry genetic information of a tumor antigen selectively to dendritic cells (DCs) in the skin. This ultimately results in the creation of CTLs designed to kill tumor cells bearing that same specific tumor antigen.
Immune Design is a clinical-stage immunotherapy company employing next-generation in-vivo approaches to enable the body's immune system to fight disease. The company's technologies are engineered to activate the immune system's natural ability to generate and/or expand antigen-specific cytotoxic T cells, while also enhancing other immune effectors, to fight cancer and other chronic diseases. CMB305 and G100, the primary focus of Immune Design's ongoing immuno-oncology clinical programs, are products of its two synergistic discovery platforms, ZVex and GLAAS, the fundamental technologies of which were licensed from the California Institute of Technology and the Infectious Disease Research Institute (IDRI), respectively. Immune Design has offices in Seattle and South San Francisco.