Dataset Information

Utilizing Immunocytokines for Cancer Therapy.

ABSTRACT: Cytokine therapy for cancer has indicated efficacy in certain diseases but is generally accompanied by severe toxicity. The field of antibody-cytokine fusion proteins (immunocytokines) arose to target these effector molecules to the tumor environment in order to expand the therapeutic window of cytokine therapy. Pre-clinical evidence has shown the increased efficacy and decreased toxicity of various immunocytokines when compared to their cognate unconjugated cytokine. These anti-tumor properties are markedly enhanced when combined with other treatments such as chemotherapy, radiotherapy, and checkpoint inhibitor antibodies. Clinical trials that have continued to explore the potential of these biologics for cancer therapy have been conducted. This review covers the in vitro, in vivo, and clinical evidence for the application of immunocytokines in immuno-oncology.

SUBMITTER: Runbeck E

PROVIDER: S-EPMC8006145 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Utilizing Immunocytokines for Cancer Therapy.

Runbeck Erin E Crescioli Silvia S Karagiannis Sophia N SN Papa Sophie S

Antibodies (Basel, Switzerland) 20210309 1

Cytokine therapy for cancer has indicated efficacy in certain diseases but is generally accompanied by severe toxicity. The field of antibody-cytokine fusion proteins (immunocytokines) arose to target these effector molecules to the tumor environment in order to expand the therapeutic window of cytokine therapy. Pre-clinical evidence has shown the increased efficacy and decreased toxicity of various immunocytokines when compared to their cognate unconjugated cytokine. These anti-tumor properties ...[more]

PMID: 33803078

Similar Datasets

Project description:Abstract BACKGROUND Glioblastoma is the most common malignant primary brain tumor in adults with an urgent need for novel treatment options. The administration of pro-inflammatory cytokines could be a potent immunotherapeutic approach to shift the balance between tumor-associated immunosuppression and immune activation. However, the systemic administration of therapeutically active doses of pro-inflammatory cytokines is not feasible due to toxic side effects and there is a need for strategies that enable a targeted delivery of pro-inflammatory cytokines to the tumor site. METHODS We investigated different antibody-cytokine fusion products that enable a targeted delivery of interleukin (IL)-2, IL-12 or tumor necrosis factor (TNF)-α to the tumor site by binding to a tumor-specific epitope of fibronectin. We investigated the expression of this tumor-specific epitope ex vivo in tumor-bearing mouse brains and human glioblastoma samples. Subsequently, we assessed the anti-tumor activity of IL-2, IL-12 or TNF-α fused to an antibody targeting this tumor-specific epitope in orthotopic syngeneic mouse glioma models. RESULTS The tumor-specfic extra domain B of fibronectin is expressed in murine glioma models and human glioblastoma samples. A fluorochrome-labeled antibody targeting this tumor-specific epitope accumulated at the tumor site in the brain in vivo upon systemic administration. IL-2, IL-12, or TNF-α fused to this antibody conferred a survival benefit in orthotopic tumor-bearing mice and cured a fraction of tumor-bearing mice. Mechanistically, antibody-fused TNF-α induced tumor necrosis and increased the activation of tumor-infiltrating natural killer (NK) cells, whereas antibody-fused IL-12 mainly boosted an anti-tumor immune response mediated by NK cells and T cells. CONCLUSION We demonstrate the expression of a tumor-specific epitope of fibronectin in glioblastoma and exploit this for the targeted delivery of IL-2, IL-12 or TNF-α to the tumor site. Our preclinical assessments indicate potent anti-tumor activity in orthotopic, syngneic glioma mouse models and reveal the mode of action for the different immunocytokines. Based on these findings, we initiated a phase I/II clinical trial in patients with recurrent glioma to investigate the targeted delivery of TNF-α (ClinicalTrials.gov identifier NCT03779230).

Dataset Information

Utilizing Immunocytokines for Cancer Therapy.

Publications

Utilizing Immunocytokines for Cancer Therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets