A Phase I Study to Evaluate the Safety and Preliminary Signs of Efficacy of [177Lu]Lu-OncoFAP-23 Alone or in Combination with L19-IL2 As a Treatment of Metastatic FAP-positive Solid Tumors

The aim of this study is to assess the safety of [177Lu]Lu-OncoFAP-23 alone or in combination with L19-IL2 for the treatment of advanced/metastatic Fibroblast Activation Protein (FAP)-positive solid tumors and to establish a Recommended Dose (RD).

开始日期2024-12-31

申办/合作机构

Philogen SpA

NCT06284590

/ Recruiting临床2期

A Phase 2, Three-arm, Randomized Study of the Efficacy of Intratumorally Administered L19IL2 or L19TNF or L19IL2/L19TNF, All in Combination with Systemic Anti-PD1 Pembrolizumab, in Stage III and IV Unresectable Melanoma Patients with Resistance to or Progressing Upon Anti-PD1 Checkpoint Inhibitors and with Presence of Injectable Metastases

The trial aims to evaluate the efficacy of single agent L19IL2, single agent L19TNF, and combination L19IL2+L19TNF given concurrently with anti-PD1 therapy compared to historical control of anti-PD-1 re-challenge alone for anti-PD1 refractory unresectable stage III-IV melanoma.

开始日期2024-07-12

申办/合作机构

Philogen SpA

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100 项与 IL-2R x EDB-FN 相关的临床结果

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100 项与 IL-2R x EDB-FN 相关的转化医学

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0 项与 IL-2R x EDB-FN 相关的专利（医药）

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项与 IL-2R x EDB-FN 相关的文献（医药）

2009-12-01·The Journal of Pathology

Impact of VEGF‐dependent tumour micro‐environment on EDB fibronectin expression by subcutaneous human tumour xenografts in nude mice

Article

作者: Giavazzi, Raffaella ; Coltrini, Daniela ; Presta, Marco ; Belleri, Mirella ; Ronca, Roberto ; Indraccolo, Stefano ; Zardi, Luciano ; Scarlato, Valentina

AbstractFibronectin (FN) is an extracellular matrix cell‐adhesive glycoprotein. The alternative spliced isoform EDB‐FN (extra domain B containing FN) is highly expressed in tumour blood vessels and stroma and represents a candidate for tumour targeting. To investigate the impact of different angiogenic micro‐environments on EDB‐FN expression, we used a tumour model in which human endometrial adenocarcinoma Tet‐FGF2 cells overexpressing fibroblast growth factor‐2 (FGF2) driven by the tetracycline‐responsive promoter were further transfected with a VEGF antisense cDNA, generating AS‐VEGF/Tet‐FGF2 cells. In this model, the expression of FGF2 plus VEGF results in fast‐growing, highly vascularized Tet‐FGF2 tumours. Down‐regulation of FGF2 production by tetracycline administration and/or of VEGF production by AS‐VEGF transduction inhibited tumour growth and vascularization, with profound changes in tumour micro‐environment. Quantitative RT‐PCR analysis using human EDB‐FN primers shows that subcutaneous grafting in immunodeficient mice is per se sufficient to cause a dramatic up‐regulation of EDB‐FN expression by these cells, as well as by human oesophageal cancer KYSE 30 cells and renal carcinoma Caki‐1 cells. However, in vivo down‐regulation of VEGF expression, as occurs in AS‐VEGF/Tet‐FGF2 tumours, and to a lesser extent of FGF2 expression, as occurs in tetracycline‐treated Tet‐FGF2 tumour‐bearing animals, causes significant inhibition of EDB‐FN production in tumour grafts, as shown by immunohistochemistry and quantitative RT‐PCR analysis. Accordingly, treatment of Tet‐FGF2 tumour‐bearing animals with the neutralizing anti‐murine VEGF receptor‐2 antibody DC101, or of Caki‐1 tumour‐bearing animals with the anti‐VEGF antibody bevacizumab, inhibited EDB‐FN expression in tumour grafts. EDB‐FN down‐regulation was paralleled by a decrease in vascularity, thus confirming EDB‐FN as a marker of tumour angiogenesis. These data demonstrate that the angiogenic micro‐environment, and in particular the VEGF/VEGFR‐2 system, plays a key role in modulating EDB‐FN expression by tumour cells in vivo. This may have implications for the design of therapeutic strategies targeting EDB‐FN in combination with anti‐angiogenic and/or cytotoxic drugs. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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