Ostroumov et al. developed a highly effective, fully synthetic, heterologous prime–single boost vaccine regimen employing a single cancer neoepitope. Systemic priming with a liposomal formulation encapsulating a STING agonist and a tumor-specific peptide antigen effectively delivered peptide antigens to and activated DCs in mice. A week later, a single systemic boost of an anti-CD40 agonistic Ab + a single synthetic tumor-specific peptide + a TLR3 or STING agonist induced rapid, massive expansion of tumor-specific T cells. In mouse cancer models, this regimen led to rapid regression and cure of large, established s.c. tumors.
Contributed by Paula Hochman
ABSTRACT: The clinical use of cancer vaccines is hampered by the low magnitude of induced T-cell responses and the need for repetitive antigen stimulation. Here, we demonstrate that liposomal formulations with incorporated STING agonists are optimally suited to deliver peptide antigens to dendritic cells in vivo and to activate dendritic cells in secondary lymphoid organs. One week after liposomal priming, systemic administration of peptides and a costimulatory agonistic CD40 antibody enables ultrarapid expansion of T cells, resulting in massive expansion of tumor-specific T cells in the peripheral blood two weeks after priming. In the MC-38 colon cancer model, this synthetic prime-boost regimen induces rapid regression and cure of large established subcutaneous cancers via the use of a single tumor-specific neoantigen. These experiments demonstrate the feasibility of liposome-based heterologous vaccination regimens to increase the therapeutic efficacy of peptide vaccines in the context of immunogenic adjuvants and costimulatory booster immunizations. Our results provide a rationale for the further development of modern liposomal peptide vaccines for cancer therapy.
Author Info: (1) Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany. (2) Department of Infectious Diseases and Immunol
Author Info: (1) Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany. (2) Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. (3) Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden, The Netherlands. (4) Department of Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands. (5) Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden, The Netherlands. (6) Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany. (7) Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany. (8) Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany. (9) Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany. (10) Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden, The Netherlands. (11) Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany. Wirth.Thomas@mh-hannover.de.
