Alpine Immune Sciences Announces Preclinical Data Showing Novel Immuno-Oncology Costimulatory Molecules Generated from vIgD Platform Fused with Trastuzumab Enhanced Immune Responses Against HER2-Positive Tumor Cells
- Category: Antibodies
- Published on Wednesday, 06 December 2017 17:10
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-- Data Presented at 2017 San Antonio Breast Cancer Symposium --
SEATTLE, WA, USA I December 6, 2017 I Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading immunotherapy company focused on developing treatments for autoimmune/inflammatory diseases and cancer, today announced results of a preclinical study of novel immuno-oncology molecules derived from the company’s variant immunoglobulin (Ig) domain (vIgD) platform. Alpine scientists fused these novel molecules with trastuzumab with the goal of activating T cells against HER2-positive tumors in the tumor microenvironment. Results showed these trastuzumab-ICOSL “V-mAbs” promoted T cell proliferation and cytokine secretion and enhanced killing of tumor cells. The data were presented in a poster session, titled “Treatment: Novel Targets and Targeted Agents (abstract # P1-09-10),” during the 40th Annual San Antonio Breast Cancer Symposium (SABCS).
Trastuzumab, known by its brand name Herceptin®, is a U.S. Food and Drug Administration-approved monoclonal antibody against HER2. It has been shown to improve survival in HER2-overexpressing cancers, including metastatic breast and gastric cancer, and when administered during adjuvant treatment for breast cancer.
“These preclinical data clearly indicate that the V-mAb format for our unique vIgD platform can yield novel HER2-targeted, T cell-activating immunotherapies,” said Stanford Peng, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Alpine. “With these findings, we are encouraged that the V-mAb format more broadly will be able to enable target- or tumor-specific immune modulation by our vIgDs for this and many other therapeutic applications.”
Preclinical Study Design and Results
Alpine scientists previously used the company’s directed evolution vIgD platform to engineer a dual ICOS/CD28 agonist (ICOSL vIgD) capable of providing a costimulatory signal when localized to targeted cells.
In patients with HER2-positive breast cancer, the presence of tumor infiltrating lymphocytes (TILs) is associated with an improved prognosis. To promote anti-tumor activity of TILs in HER2-positive tumors, Alpine fused ICOSL vIgDs to trastuzumab, generating trastuzumab-ICOSL V-mAbs. Alpine used various in vitro and in vivo tests to characterize the functional activity of these V-mAbs. Results showed they:
- Retained binding to CD28, ICOS, and HER2.
- Demonstrated in vitro proof of principle for T cell stimulation and proliferation in response to HER2-positive tumor cells – i.e., they enhanced interferon-gamma production, promoted CD4 T cell and CD8 T cell proliferation, and promoted cell lysis (tumor killing).
“These preclinical results add to the growing body of data suggesting our versatile vIgD platform has the unique potential to create the next generation of immuno-oncology therapeutics with novel mechanisms of action when fused with already-approved monoclonal antibodies,” said Mitchell H. Gold, M.D., Executive Chairman and Chief Executive Officer of Alpine. “We continue to identify, develop, and evaluate candidates from our vIgD platform for oncology and inflammatory indications.”
About Alpine Immune Sciences, Inc.
Alpine Immune Sciences, Inc. is focused on developing novel protein-based immunotherapies using its proprietary Variant Ig Domain (vIgD) platform technology. The vIgD platform is designed to interact with multiple targets, including many present in the immune synapse. Alpine’s vIgDs are developed using a process known as directed evolution, which produces proteins capable of either enhancing or diminishing an immune response and thereby may potentially apply therapeutically to cancer, autoimmune and inflammatory diseases. Alpine has also developed Transmembrane Immunomodulatory Protein (TIP) technology, based on the vIgD platform, to potentially enhance engineered cellular therapies. For more information, visit www.alpineimmunesciences.com.
SOURCE: Alpine Immune Sciences