On 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 (Press release, Repertoire, APR 27, 2022, View Source [SID1234613072]). 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).
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"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.