Trial watch

Abstract

Tumor-targeting immune responses provide a significant contribution to (when they do not entirely account for) the clinical activity of diverse antineoplastic regimens, encompassing not only a large panel of immunotherapeutic strategies but also conventional cytotoxic molecules, targeted anticancer agents and irradiation. In line with this notion, several approaches have been devised to elicit novel or boost existing anticancer immune responses, including the administration of immunomodulatory cytokines. Such a relatively unspecific intervention suffices to mediate clinical effects in (at least a subset of) patients bearing particularly immunogenic tumors, like melanoma and renal cell carcinoma. More often, however, immunostimulatory cytokines are administered to boost the immunogenic potential of other agents, including (but not limited to) immune checkpoint-blocking antibodies, anticancer vaccines, oncolytic viruses and immunogenic chemotherapeutics. Here, we summarize the latest advances in the clinical development of recombinant cytokines as an immunomodulatory intervention for cancer therapy.

He-Wei granules (HWKL) combat cisplatin-induced nephrotoxicity and myelosuppression in rats by inhibiting oxidative stress, inflammatory cytokines and apoptosis

“…In addition, there is increasing evidence which indicates that cisplatin induces a wide variety of inammatory cytokines and chemokines including translocation of the redox-sensitive transcription factor NF-kB from the cytosol to the nucleus. [47][48][49][50] As a result, the expression of several proinammatory genes, including IL-1b, TNF-a and COX-2, was triggered. In the inammatory response triggered by cisplatin, TNF-a appears to be a key upstream regulator.…”

TNFa and IL-2 armed adenoviruses enable complete responses by anti-PD-1 checkpoint blockade

“…When studying the tumor microenvironment, it has been claimed that intratumoral injection of cytokines can result in tumor control or beneficial effects on the tumor microenvironment 23,50,51 with no need of specific cell populations able to produce those cytokines. In this regard, viruses are a convenient tool to deliver cytokines locally, resulting in extended high level expression without significant systemic exposure.…”

The Interactions Between Cancer Stem Cells and the Innate Interferon Signaling Pathway

“…Intensive research focused on IFNs' anti-tumor activities finally led to the approval of IFN-α by the FDA as the first cancer immunotherapy in 1986 (103). In spite of being discovered for their anti-viral activities, IFN-α2a and IFN-α2b have been used as anticancer therapeutic agents across multiple cancer types, including hairy cell leukemia, chronic myelogenous leukemia (CML) (104), AIDS-related Kaposi's sarcoma, follicular lymphoma, multiple myeloma, melanoma, condyloma acuminate, hepatocellular carcinoma (HCC), and cervical intraepithelial neoplasms (105,106). IFN-β use as an anticancer drug is still under study, although ongoing phase III trials for melanoma (107,108) and for glioma (109) and glioblastoma (110) are being conducted with promising results.…”