ALG.APV-527 activates and enhances T cells and NK cells

Alligator Bioscience and Aptevo Therapeutics presented on potential therapeutic at SITC annual meeting

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LUND, Sweden & SEATTLE—Alligator Bioscience, a biotechnology company developing antibody-based pharmaceuticals for tumor-directed immunotherapy, and Aptevo Therapeutics Inc., a biotechnology company focused on developing novel immuno-oncology and hematology therapeutics, announced late last year that new preclinical data for ALG.APV-527 were being presented at the Society for Immunotherapy of Cancer's (SITC) 33rd Annual Meeting held in Washington, D.C.
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 antitumor 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 non-small cell lung cancer, head and neck cancer, mesothelioma, pancreatic cancer, bladder cancer, renal cancer 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 Dr. Christina Furebring, 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 nine days, and good manufacturing properties,” added Dr. Jane Gross, chief scientific officer for Aptevo. “Aptevo and Alligator believe that ALG.APV-527 has the potential to be a unique anticancer 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.”   
ALG.APV-527 is a bispecific antibody (4-1BB x 5T4) intended for tumor-directed treatment of solid cancers. It 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.

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