Immune Design Presents Data on the Mechanism of Action of G100 via TLR4 Expressed in B Cell Malignancies at the Inaugural AACR International Meeting Advances in Malignant Lymphoma
- G100 directly targets and modifies TLR4 expressing malignant B cells making them more visible to the anti-tumor immune response-
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
The full poster presentation can be accessed from the publications page of the
G100 is a product candidate from
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Source: Immune Design Corp.