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High-Affinity PD-L1 Antibodies for the Treatment of Cancer

High-affinity PD-L1 monoclonal antibodies using light chain shuffling enhances cancer treatment effectiveness

  • Therapeutics

Project Overview

  • Blockade of immune checkpoints programmed death-1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1) is garnering increased attention in the field of cancer immunotherapy, particularly the application of PD-1/PD-L1 monoclonal antibodies.
  • Scientists at Dana-Farber have invented a method of use of isolated monoclonal antibodies against PD-L1.
  • Dana-Farber is seeking an Exclusive License for this technology.

Technology

Programmed death-1 (PD-1) is a cell surface membrane protein and a member of the CD28 family that functions as an immune checkpoint, which can suppress immune responses and prevent the activation of T cells from attacking cancer cells. Blockade of immune checkpoints PD-1 and its ligand, programmed death-ligand 1 (PD-L1), is therefore garnering increased attention in the field of cancer immunotherapy, particularly the application of PD-1/PD-L1 monoclonal antibodies.

The structure of an antibody consists of four polypeptide chains comprising two heavy chains (each weighing ~50 kDa) and two light chains (~25 kDa each), and each chain is further composed of a constant region and a variable region that are distinguished based on amino acid similarity. This invention is directed to methods of use of isolated monoclonal antibodies against PD-L1.

This invention by Dr. Wayne Marasco, Principal Investigator, Cancer Immunology and Virology, at Dana-Farber addresses the need for monoclonal antibodies that bind to PD-L1 with higher affinity. Such antibodies were created to comprise a heavy chain, light chain, or a combination thereof. Since the heavy chains strongly contribute to antibody binding specificity, heavy chain variable regions were fused with light chain variable regions to form new light chain shuffling (LCS) libraries using the LCS technique. The novel antibody LCS libraries each possess ~2x10E8 diversity. Furthermore, the new LCS libraries were panned with decreased antigen concentration, leading to the identification of higher-affinity PD-L1 antibodies. The invention is directed to a method of treating cancer and provides an improvement over previous antibodies with lower affinity for PD-L1.

Team Members: Wayne Marasco, MD, PhD, Quan Karen Zhu, PhD, Eric Peterson

Applications

The antibodies can be used with higher affinity against immune modulators, such as PD-L1, to treat cancer, as well as chronic viral infections.

Opportunities

Dana-Farber Cancer Institute is looking for the right partner with an interest in licensing these assets for further development into new oncology therapeutics.

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Team Members