Intravenous injection of a modified vaccinia ankara virus induces intratumoral CD8+ lymphocyte infiltration favoring tumor control in an orthotopic tumor model upon combinatorial treatment with a TLR9 agonist
نویسندگان
چکیده
Background There are many critical steps for the clinical efficacy of antigen-specific T cell-based immunotherapies among which traffic to and access to tumor beds of effector T cells, are the most limiting [1]. Preclinical research most often uses ectopic mouse tumor models for the readout fastness and easiness provided by such models. However, those models may not be the optimal way to address the issue of targeting effector T cells to a deep organ born tumor.
منابع مشابه
Shaping the tumor microenvironment with Modified Vaccinia Virus Ankara and TLR9 ligand
Our preclinical data demonstrate that an intravenous injection of Modified Vaccinia virus Ankara induces CD8+ lymphocytes to infiltrate organs to control the growth of orthotopic renal carcinoma upon combination with a toll-like receptor 9 agonist. Such shaping of the tumor microenvironment could constitute the basis of more effective clinical protocols of tumor immunotherapy.
متن کاملIntravenous injection of MVA virus targets CD8+ lymphocytes to tumors to control tumor growth upon combinatorial treatment with a TLR9 agonist.
Effector T-cell access to tumor tissue is a limiting step for clinical efficacy of antigen-specific T cell-based immunotherapies. Ectopic mouse tumor models, in which a subcutaneously (s.c.) implanted tumor is treated with s.c. or intramuscular therapeutic immunization, may not be optimal for targeting effector T cells to an organ-borne tumor. We used an orthotopic renal carcinoma model to eval...
متن کاملIntratumoral injection of a CpG oligonucleotide reverts resistance to PD-1 blockade by expanding multifunctional CD8+ T cells.
Despite the impressive rates of clinical response to programmed death 1 (PD-1) blockade in multiple cancers, the majority of patients still fail to respond to this therapy. The CT26 tumor in mice showed similar heterogeneity, with most tumors unaffected by anti-PD-1. As in humans, response of CT26 to anti-PD-1 correlated with increased T- and B-cell infiltration and IFN expression. We show that...
متن کاملImmunotherapeutic synergy between anti-CD137 mAb and intratumoral administration of a cytopathic Semliki Forest virus encoding IL-12.
Intratumoral injection of Semliki Forest virus encoding interleukin-12 (SFV-IL-12) combines acute expression of IL-12 and stressful apoptosis of infected malignant cells. Agonist antibodies directed to costimulatory receptor CD137 (4-1BB) strongly amplify pre-existing cellular immune responses toward weak tumor antigens. In this study, we provide evidence for powerful synergistic effects of a c...
متن کاملModified vaccinia virus Ankara induces Toll-like receptor-independent type I interferon responses.
Modified vaccinia virus Ankara (MVA) is a highly attenuated vaccinia virus strain undergoing clinical evaluation as a replication-deficient vaccine vector against various infections and tumor diseases. To analyze the basis of its high immunogenicity, we investigated the mechanism of how MVA induces type I interferon (IFN) responses. MVA stimulation of bone marrow-derived dendritic cells (DC) sh...
متن کامل