"Background: mRNA-4359 is a lipid nanoparticle encapsulated mRNA-based cancer vaccine encoding for concatemerized program death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) antigens given as an intramuscular injection. These proteins are found across a wide range of cancer types. PD-L1 is a cell surface receptor expressed on both tumor and regulatory immune cells and functions as a checkpoint to inhibit T cell function, while IDO1 is an L-tryptophan metabolizing enzyme involved in T cell suppression and immune tolerance. Both are thought to impart an inhibitory tumor microenvironment which allows tumor cells to escape immune monitoring and clearance. T cells that can target PD-L1 and IDO1 are known to pre-exist in cancer patients and a recent study leveraging a peptide-based vaccine approach demonstrated they can be induced to elicit clinically meaningful and durable tumor responses in patients with metastatic melanoma when combined with PD-1 inhibition. mRNA-4359 encodes immunogenic peptides proposed to generate anti-PD-L1/IDO1-specific T-cells to kill immunosuppressive regulatory cells as well as cancer cells which express those antigens and thus tip the balance towards an inflammatory and/or immune permissive tumor microenvironment. Additionally, combination with checkpoint inhibition may further amplify this anti-tumor immunostimulatory effect, resulting in superior clinical outcomes. "
"Background: mRNA-4359 is a lipid nanoparticle encapsulated mRNA-based cancer vaccine encoding for concatemerized program death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) antigens given as an intramuscular injection. These proteins are found across a wide range of cancer types. PD-L1 is a cell surface receptor expressed on both tumor and regulatory immune cells and functions as a checkpoint to inhibit T cell function, while IDO1 is an L-tryptophan metabolizing enzyme involved in T cell suppression and immune tolerance. Both are thought to impart an inhibitory tumor microenvironment which allows tumor cells to escape immune monitoring and clearance. T cells that can target PD-L1 and IDO1 are known to pre-exist in cancer patients and a recent study leveraging a peptide-based vaccine approach demonstrated they can be induced to elicit clinically meaningful and durable tumor responses in patients with metastatic melanoma when combined with PD-1 inhibition. mRNA-4359 encodes immunogenic peptides proposed to generate anti-PD-L1/IDO1-specific T-cells to kill immunosuppressive regulatory cells as well as cancer cells which express those antigens and thus tip the balance towards an inflammatory and/or immune permissive tumor microenvironment. Additionally, combination with checkpoint inhibition may further amplify this anti-tumor immunostimulatory effect, resulting in superior clinical outcomes. "