Repertoire’s proprietary cell-tethering technology limits systemic toxicity typically associated with use of immunomodulatory IL-12 and allows direct delivery to solid tumors in mouse models

Tethered IL-12 repolarizes the tumor microenvironment potentially creating improved conditions for cellular immunotherapies to work effectively

CAMBRIDGE, Mass. – April 27, 2022 – Repertoire Immune Medicines announced today that Science Advances published preclinical research demonstrating the company’s cell-tethering technology can deliver the potent cytokine interleukin-12 (IL-12) to solid tumors without eliciting the severe systemic toxicities typically associated with the use of this cytokine. The research, conducted in mouse models, found that the use of cell-tethered IL-12 elevated anti-tumor activity in the immunosuppressive tumor microenvironment (TME).

“A tumor has multiple mechanisms that help it avoid recognition and elimination by the immune system. These defense mechanisms remain a major challenge for cellular immunotherapies to achieve a durable clinical response,” said Anthony Coyle, Ph.D., President, Research and Development, Repertoire Immune Medicines. “In this preclinical research, Repertoire’s cell-tethering technology delivered dose-controlled amounts of IL-12 onto the surface of tumor-targeted T cells. These IL-12-tethered T cells were associated with pronounced repolarization of the tumor microenvironment, ultimately resulting in enhanced T cell response, which has the potential to improve the efficacy of the cellular immunotherapies.”

Tumors have immunosuppressive microenvironments that can limit the efficacy of cellular immunotherapies used in cancer treatment. Immune-stimulating cytokines such as IL-12 have been shown to counter the immunosuppressive conditions within the tumor. However, the dose of IL-12 required to achieve these beneficial effects has been associated with severe systemic toxicities.

In the publication, “Cell-surface tethered IL-12 repolarizes the tumor immune microenvironment to enhance the efficacy of adoptive T cell therapy,” Repertoire’s tethering technology achieved direct and localized delivery of IL-12 to tumors without systemic toxicities. The use of tethered IL-12 was also associated with repolarization of myeloid-derived suppressor cells into activated inflammatory monocytes that support anti-tumor activity in the TME.

Repertoire is currently investigating the use of cell-tethered IL-12 in an ongoing Phase 1 study of its investigational candidate RPTR-168 for human papillomavirus-positive tumors.

About RPTR-168

RPTR-168 is an autologous multi-targeted T cell (MTC) therapeutic candidate derived from rare peripheral blood T cells. The T cells are collected from each patient through apheresis and are primed and expanded by a set of five tumor-associated antigens known to be expressed on human papillomavirus (HPV)-16-positive tumors. RPTR-168 is designed to deliver interleukin-12 (IL-12), a potent immunomodulatory agent that has been shown to improve anti-tumor activity by promoting T cell function inside the tumor microenvironment.

About Repertoire Immune Medicines

Repertoire Immune Medicines is a clinical-stage biotechnology company dedicated to creating treatments for diseases based on the power of the human T cell repertoire to eliminate cancer cells, target pathogens and regulate immune function.

Repertoire’s strategy lies in understanding the immune synapse – the interaction between specific T cells and the corresponding antigen-presenting cells that dictate T cell activity. The company’s proprietary DECODE™ technology platform, developed by Repertoire scientists, provides a comprehensive understanding of the full repertoire of interactions between T cell receptors and their antigen targets. We believe the ability to decode these interactions represents one of the greatest opportunities for innovation in medical science.

Repertoire’s team operates from sites in Cambridge, Massachusetts and Zurich, Switzerland and uses its DECODE technology to rationally design treatments for cancers, autoimmune disorders and infectious diseases.