L19-IL2 Immunocytokine in Combination with the Anti-Syndecan-1 46F2SIP Antibody Format: A New Targeted Treatment Approach in an Ovarian Carcinoma Model

Orecchia, Paola; Balza, Enrica; Pietra, Gabriella; Conte, Romana; Bizzarri, Nicolò; Ferrero, Simone; Mingari, Maria Cristina; Bárbara, Cristina

doi:10.3390/cancers11091232

Cited by 15 publications

(10 citation statements)

References 57 publications

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“…Two forms of antibody therapeutics targeting GPC2 have been successfully developed for neuroblastoma treatment [247]. The human antibody OC-46F2, specific for the ectodomain domain of SDC1, has proved to inhibit tumor growth in experimental human models of melanoma and ovarian carcinoma by blocking angiogenesis [193,248]. In some cases, antibody-drug-conjugates (ADC) consisting of a highly cytotoxic small-molecule covalently linked to a monoclonal antibody that recognizes a cell surface antigen have been developed.…”

Section: Heparan Sulfate Proteoglycans As Therapeutic Targets For Cancermentioning

confidence: 99%

Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment

Pasquale

Pavone

2020

IJMS

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In the last few decades, heparan sulfate (HS) proteoglycans (HSPGs) have been an intriguing subject of study for their complex structural characteristics, their finely regulated biosynthetic machinery, and the wide range of functions they perform in living organisms from development to adulthood. From these studies, key roles of HSPGs in tumor initiation and progression have emerged, so that they are currently being explored as potential biomarkers and therapeutic targets for cancers. The multifaceted nature of HSPG structure/activity translates in their capacity to act either as inhibitors or promoters of tumor growth and invasion depending on the tumor type. Deregulation of HSPGs resulting in malignancy may be due to either their abnormal expression levels or changes in their structure and functions as a result of the altered activity of their biosynthetic or remodeling enzymes. Indeed, in the tumor microenvironment, HSPGs undergo structural alterations, through the shedding of proteoglycan ectodomain from the cell surface or the fragmentation and/or desulfation of HS chains, affecting HSPG function with significant impact on the molecular interactions between cancer cells and their microenvironment, and tumor cell behavior. Here, we overview the structural and functional features of HSPGs and their signaling in the tumor environment which contributes to tumorigenesis and cancer progression.

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Section: Heparan Sulfate Proteoglycans As Therapeutic Targets For Cancermentioning

confidence: 99%

Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment

Pasquale

Pavone

2020

IJMS

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“…Collagen IV is a component of the basement membrane of the VM tube and also promotes VM tube formation [21]. Further, targeting the abnormally secreted proteoglycan SDC1 in ovarian cancer can inhibit tumor cells from forming tubule-like structures in vitro and in vivo [203]. In addition, ECM components can further affect the differentiation direction of CSCs.…”

Section: Hypoxia Promotes Vasculogenic Mimicry Network Formation By Pmentioning

confidence: 99%

Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments

et al. 2021

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Background Vasculogenic mimicry (VM) is a recently discovered angiogenetic process found in many malignant tumors, and is different from the traditional angiogenetic process involving vascular endothelium. It involves the formation of microvascular channels composed of tumor cells; therefore, VM is considered a new model for the formation of new blood vessels in aggressive tumors, and can provide blood supply for tumor growth. Many studies have pointed out that in recent years, some clinical treatments against angiogenesis have not been satisfactory possibly due to the activation of VM. Although the mechanisms underlying VM have not been fully elucidated, increasing research on the soil “microenvironment” for tumor growth suggests that the initial hypoxic environment in solid tumors is inseparable from VM. Main body In this review, we describe that the stemness and differentiation potential of cancer stem cells are enhanced under hypoxic microenvironments, through hypoxia-induced epithelial-endothelial transition (EET) and extracellular matrix (ECM) remodeling to form the specific mechanism of vasculogenic mimicry; we also summarized some of the current drugs targeting VM through these processes, suggesting a new reference for the clinical treatment of tumor angiogenesis. Conclusion Overall, the use of VM inhibitors in combination with conventional anti-angiogenesis treatments is a promising strategy for improving the effectiveness of targeted angiogenesis treatments; further, considering the importance of hypoxia in tumor invasion and metastasis, drugs targeting the hypoxia signaling pathway seem to achieve good results.

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“…Immunocytokine alone, and to a greater extent with rituximab, increased macrophage and NK cell presence in the tumor compared to controls [ 170 ]. An antibody targeting syndecan-1 inhibited vascular tubule formation, and when co-administered with this EDB-targeting immunocytokine, melanoma tumors were ablated in ~71% of mice and a significant reduction occurred in ovarian tumor progression [ 171 , 172 ]. Targeted TNF to the melanoma antigen gp75 in combination with a monoclonal antibody of the same specificity augmented the efficacy in syngeneic melanoma models compared to either therapy alone.…”

Section: Immunocytokines In Combination Therapeutic Approachesmentioning

confidence: 99%

Utilizing Immunocytokines for Cancer Therapy

et al. 2021

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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.

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L19-IL2 Immunocytokine in Combination with the Anti-Syndecan-1 46F2SIP Antibody Format: A New Targeted Treatment Approach in an Ovarian Carcinoma Model

Cited by 15 publications

References 57 publications

Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment

Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment

Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments

Utilizing Immunocytokines for Cancer Therapy

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