Alligator Bioscience and Aptevo Therapeutics Present New Preclinical Data for ALG.APV-527 at the Society for Immunotherapy of Cancer (SITC) 33rd Annual Meeting
Data Show That ALG.APV-527 Selectively Activates and Enhances Tumor-directed T-cell and Natural Killer (NK) Cell Responses
Targets 5T4 Cancer Antigen Present on Many Types of Solid Tumors
LUND, Sweden and SEATTLE,
ALG.APV-527 is a new immunotherapeutic candidate for the treatment of a variety of 5T4-positive solid tumors. It is designed to induce signaling through the co-stimulatory receptor 4-1BB (CD137), which is present on activated cytotoxic T cells and natural killer (NK) cells. Once activated, it is designed to promote potent and selective tumor-directed immune activation in the presence of 5T4 antigen-expressing tumor cells, which are present on many different types of solid tumors.
The preclinical data show that ALG.APV-527 localizes to 5T4 positive tumors and selectively stimulates and enhances tumor-directed T-cell and NK cell responses, displaying potent anti-tumor effects. Notably, the preclinical in vitro data demonstrated that in the presence of 5T4-positive cells, ALG.APV-527:
- Increases CD8+ cytotoxic T cells’ ability to secrete the pro-inflammatory cytokine IFN-g production, but only in the presence of human tumor cells that display 5T4 at their surface
- Enhances the cytotoxic profile of NK cells
Additionally, these new data confirm that 5T4 antigen is present on a wide range of tumor types. 5T4-positive tumor cells were detected in tumor samples from NSCLC (non-small cell lung cancer), head and neck, mesothelioma-, pancreatic-, bladder-, renal- and ovarian cancer, but not in normal tissues such as liver or heart.
“The latest preclinical data further strengthen ALG.APV-527’s potential to localize to 5T4-expressing tumors, where it selectively can activate the immune system and enhance tumor specific T cell or NK activation at the tumor site, potentially providing a favorable safety profile while enhancing efficacy. We are currently compiling a preclinical package with the goal of submitting a clinical trial application (CTA) in late 2019,” said Christina Furebring Ph.D., Senior Vice President Research at Alligator.
“Our novel bispecific candidate, ALG.APV-527, continues to show promising results in preclinical in vitro and in vivo studies. Featuring target-driven T-cell activation, optimized stability, an antibody-like serum half-life of 9 days, and good manufacturing properties. Aptevo and Alligator believe that ALG.APV-527 has the potential to be a unique anti-cancer therapeutic for the treatment of numerous 5T4-expressing solid tumors with high unmet medical need. We look forward to filing the CTA next year and commencing clinical study of this promising immunotherapy,” said Jane Gross, Ph.D., Chief Scientific Officer for Aptevo.
The Alligator/Aptevo poster presentation, entitled “Potent Tumor-Directed T Cell Activation and Tumor Inhibition Induced by a 4-1BB x 5T4 ADAPTIR™ Bispecific Antibody” is being presented
For further information, please visit https://www.sitcancer.org/2018/home.
ALG.APV-527 is a bispecific antibody (4-1BB x 5T4) intended for tumor-directed treatment of solid cancers. ALG.APV-527 was built using Aptevo’s ADAPTIR™ bispecific platform and combines binding domains sourced from the ALLIGATOR-GOLD® human scFV library. The ALG.APV-527 bispecific antibody consists of two parts, one part activating tumor-specific T cells through the co-stimulatory receptor 4-1BB, the other part binding to the 5T4 protein displayed on the surface of tumor cells. This enables the immune-activating effect of ALG.APV-527 to be directed specifically to the tumor and not against normal tissue.
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