Date: 2018-06-25
Type of
information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the American Association for Cancer Research (AACR) Annual Meeting
Company: Immune Design (USA - MA)
Product: G100
Action
mechanism:
- immunotherapy product. 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 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.
Disease: indolent non-Hodgkin Follicular lymphomas (FL)
Therapeutic
area: Cancer - Oncology
Country:
Trial
details:
Latest
news:
- • On June 25, 2018, Immune Design announced preclinical and translational data that support the mechanism of action of G100 in patients with indolent non-Hodgkin Follicular lymphomas (FL). These data were presented at the Inaugural AACR International Meeting Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application 2018 in Boston.
- The research presented was designed to understand why high TLR 4 expression in patient’s samples correlated with clinical responses to G100 treatment. By analyzing patient samples, cell lines and mouse lymphoma models the following was observed:
- Murine and human B-lymphoma cell lines express TLR4 and respond in vitro to G100 stimulation with upregulation of MHC-II and co-stimulatory markers CD40 and CD80, typical of the activation of antigen-presenting function of B-cells;
- In vivo murine tumors of lymphoma models respond to treatment with G100 in injected tumors as well as distal, untreated tumors showing local and abscopal tumor control, mediated by systemic T-cell response;
- Approximately 70% of follicular lymphoma patients in a Phase 1/2 study express TLR4 in >50% of tumor cells in baseline biopsies. TLR4 expression ranging from 10%-100% of tumor cells was also detected in biopsies of patients with marginal zone lymphoma, small lymphocytic lymphoma, diffuse large B-cell lymphoma and cutaneous T-cell lymphoma; and
- In an ongoing Phase 2 trial of G100 with low dose radiation and pembrolizumab, almost all patients with an objective tumor response (³50% tumor shrinkage) showed TLR4 expression in >50% of tumor cells.
- “These data illustrate that in addition to the known activation by G100 of dendritic cells and macrophages in the tumor microenvironment, G100 can also act directly on malignant B cells expressing TLR4. G100 treated malignant B cells may become more visible to the anti-tumor immune response, which correlates with clinical responses following intratumoral therapy with G100.” said Jan ter Meulen, MD, PhD, Chief Scientific Officer at Immune Design. “In FL patients, a strong correlation was observed between expression of TLR4 in more than 50% of tumor cells and objective responses following G100 therapy. This discovery potentially allows for a TLR4 biomarker-targeted G100 therapy of other tumor types, independent of histology.”
Is
general: Yes
