Virotherapy and checkpoint inhibitors can be combined for the treatment of cancer with complementarity and potential for synergistic effects. We have developed a cytolytic but nonreplicative viral vector system based on Semliki Forest virus that encodes IL12 (SFV-IL12). Following direct intratumoral injection, infected cells release transgenic IL12, die, and elicit an inflammatory response trig...

Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) is a root cause of lethality in patients. The metastasis promoted by abundant proteases the PDAC microenvironment. Synthetic immuno-oncology opens new avenues towards overcoming limitations standard immunotherapy agents, previously unsuccessful PDAC. Anti-tumour cytokines such as IL-12 poorly infiltrate stroma solid tumours and trigger toxicity...

OBJECTIVE The goal of this study was to investigate the role of endogenous interleukin 12 (IL12) in acute murine streptococcal cell wall (SCW) arthritis. METHODS C57black/6 mice were injected intraperitoneally with rat anti-murine IL12 (C17.8), shortly before induction of arthritis by intra-articular injection of 25 microg SCW fragments into the right knee joint. Joint swelling and chondrocyt...

PURPOSE Infusion of interleukin-12 (IL12) can mediate antitumor immunity in animal models, yet its systemic administration to patients with cancer results in minimal efficacy and severe toxicity. Here, we evaluated the antitumor activity of adoptively transferred human tumor-infiltrating lymphocytes (TILs) genetically engineered to secrete single-chain IL12 selectively at the tumor site. EXPE...

OBJECTIVES Replication-competent, vesicular stomatitis virus (VSV) has been demonstrated to be an effective oncolytic agent in a variety of malignant tumors. Cytokine gene transfer has also been used as immunomodulatory therapy for cancer. To test the use of combining these two approaches, an oncolytic VSV vector (rVSV-IL12) was designed to express the murine interleukin 12 (IL12) gene. This cy...

OBJECTIVES The aim of this study was to evaluate serum interleukin (IL) 12 concentration in patients with juvenile chronic arthritis (JCA), according to disease subtype, activity, and duration. IL12 has been demonstrated to prime the selective expansion of T helper (Th) cells with a Th1-type pattern of cytokine production. METHODS Sixty eight serum samples from 50 JCA patients (12 systemic, 1...

BACKGROUND Interleukin (IL)-12 is a pro-inflammatory cytokine that mediates T-helper type 1 responses and cytotoxic T-cell activation, contributing to its utility as anti-cancer agent. Systemic administration of IL-12 often results in unacceptable toxicity; therefore, strategies to direct delivery of IL-12 to tumors are under investigation. The objective of this study was to assist the preclini...

Both adoptive immunotherapy and gene therapy hold a great promise for treatment of malignancies. However, these strategies exhibit limited anti-tumor activity, when they are used alone. In this study, we explore whether combination of cytokine-induced killer (CIK) adoptive immunotherapy with oncolytic adenovirus-mediated transfer of human interleukin-12 (hIL-12) gene induce the enhanced antitum...

Mesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of malignant mesothelioma. Monoclonal antibodies against mesothelin are being evaluated for the treatment of mesothelioma. Immunocytokines represent a novel class of armed antibodies. To provide an alternative approach to current mesothelin-targeted antibody therapies, we have develop...

PURPOSE We investigated whether an armed viral platform, where lytic property of a viral infection is coupled to viral-mediated delivery of therapeutic genes, could increase the therapeutic potential of a viral-based therapy. EXPERIMENTAL DESIGN We generated interleukin (IL)-12-expressing oncolytic adenovirus (YKL-IL-12) and IL-12- and B7-1-expressing (YKL-IL12/B7) oncolytic adenovirus. Thera...