scholarly journals AXL targeting by a specific small molecule or monoclonal antibody inhibits renal cell carcinoma progression in an orthotopic mice model

2021 ◽  
Vol 9 (23) ◽  
Author(s):  
Tony J. Chen ◽  
Piotr Mydel ◽  
Małgorzata Benedyk‐Machaczka ◽  
Marta Kamińska ◽  
Urszula Kalucka ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Monoclonal Antibody ◽  
Cell Carcinoma ◽  
Small Molecule ◽  
Renal Cell ◽  
Mice Model

scholarly journals Newly-presented potential targeted drugs in the treatment of renal cell cancer

2016 ◽  
Vol 11 (1) ◽  
pp. 122-129
Author(s):  
Jingfeng Zhang ◽  
Qinsi He ◽  
Zhi Zheng
Keyword(s):  
Renal Cell Carcinoma ◽  
Monoclonal Antibody ◽  
Cell Carcinoma ◽  
Small Molecule ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Cell Cancer ◽  
Targeted Drugs ◽  
Cell Renal Cell Carcinoma ◽  
Targeted Treatments

AbstractRenal cell carcinoma (RCC) is the most frequent form of renal cancer, and is associated with a high frequency of metastasis. While, there is few therapeutic methods can substantially prolong survival. Superior to cytokine therapy with IL-2 and/or IFN-a, several newer targeted treatments are available for the treatment of patients with advanced conventional (clear cell) renal cell carcinoma (RCC), which received improved outcomes. These newer targeted treatments include the multi-targeted tyrosine kinase inhibitors (TKIs, sorafenib, sunitinib, pazopanib, and axitinib), the humanised antivascular endothelial growth factor (VEGF) monoclonal antibody [bevacizumab combined with interferon (IFN)-a], and mTOR (mammalian target of rapamycin) complex 1 kinase inhibitors (everolimus and temsirolimus). However, these targeted drugs are still associated with limited efficacy and high toxicity, so there is still a strong need for further discovery of new targeted drugs. In the present manuscript, we summarize newly-presented potential targeted drugs for RCC, classified by drug characteristic, small molecule, small molecule combination, monoclonal antibody, polysaccharides, organometals and peptides.

12 Phase II study of lutetium-177-labeled anti carbonic anhydrase IX monoclonal antibody girentuximab in patients with advanced renal cell carcinoma

2015 ◽  
Vol 14 (2) ◽  
pp. e12 ◽  
Author(s):  
C.H.J. Muselaers ◽  
T.J. Van Oostenbrugge ◽  
M.J. Boers-Sonderen ◽  
O.C. Boerman ◽  
I.M.E. Desar ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Monoclonal Antibody ◽  
Carbonic Anhydrase ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Phase Ii Study ◽  
Carbonic Anhydrase Ix ◽  
Advanced Renal Cell Carcinoma

scholarly journals Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250.

1997 ◽  
Vol 15 (4) ◽  
pp. 1529-1537 ◽  
Author(s):  
M G Steffens ◽  
O C Boerman ◽  
J C Oosterwijk-Wakka ◽  
G O Oosterhof ◽  
J A Witjes ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Monoclonal Antibody ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Primary Tumors ◽  
Chimeric Monoclonal Antibody ◽  
Imaging Characteristics ◽  
Iodine 131 ◽  
Dosimetric Analysis

PURPOSE Pharmacokinetics, biodistribution, immunogenicity, and imaging characteristics of iodine 131 (131I)-labeled chimeric monoclonal antibody (mAb) G250 (cG250) were studied in patients with renal cell carcinoma (RCC) to determine the therapeutic potential of this antibody. PATIENTS AND METHODS Sixteen patients with RCC received a single intravenous (IV) infusion of 6 mCi 131I-labeled cG250. Five protein dose levels were investigated (2 to 50 mg). Planar scintigraphic images were acquired, and normal tissue biopsies and tumor samples were obtained of surgery (7 days postinjection). The immunogenicity of cG250 was investigated using a sandwich enzyme-linked immunosorbent assay (ELISA) and dosimetric analysis was performed. RESULTS In all patients with antigen-positive tumors (n = 13), the primary tumors and all known metastases were clearly visualized. Overall uptake, expressed as the percentage of the injected dose (%ID), in the primary tumors ranged from 2.4 to 9.0. Focally, 131I-cG250 uptake as high as 0.52% ID/g was observed. However, intratumoral uptake was highly heterogeneous. 131I-cG250 uptake in nontumorous tissues remained low. Dosimetric analysis showed that up to .48 Gy/mCi was guided to the primary tumors. Selected "hot areas" within these tumors received up to .72 Gy/mCi. A bone metastasis received .23 Gy/mCi and regional lymph node metastases received .20 Gy/mCi. Minimal human antichimeric antibody (HACA) levels were detected in two of 16 patients. CONCLUSION 131I-cG250 tumor uptake is among the highest reported in clinical studies with antitumor antibodies in solid tumors. Since tumor-sterilizing levels may be guided to the tumor when high doses 131I-cG250 are administered (> 100 mCi) and cG250 appears to be immunosilent, cG250 is a promising vehicle for radioimmunotherapy in RCC.

Antibody localization in human renal cell carcinoma: a phase I study of monoclonal antibody G250.

1993 ◽  
Vol 11 (4) ◽  
pp. 738-750 ◽  
Author(s):  
E Oosterwijk ◽  
N H Bander ◽  
C R Divgi ◽  
S Welt ◽  
J C Wakka ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Monoclonal Antibody ◽  
Cell Surface ◽  
Cell Carcinoma ◽  
Surface Antigen ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Surface Antigen ◽  
Human Renal Cell Carcinoma ◽  
A Cell

PURPOSE To define the imaging and biodistribution characteristics of iodine 131-labeled monoclonal antibody (mAb) G250 (131I-mAbG250), which recognizes a cell-surface antigen expressed by human renal cell carcinoma (RCC). PATIENTS AND METHODS G250 is a cell-surface antigen recognized by mAbG250 expressed by RCC but not detected in normal kidney. Clear-cell RCC, the most frequent form of RCC, shows homogeneous expression of G250, whereas non-clear-cell RCC and cancers derived from other organs generally do not express G250. Expression in normal tissues is highly restricted and limited to large bile ducts and gastric epithelium. 131I-mAbG250 was administered intravenously (IV) to 16 patients with RCC 7 to 8 days before surgery at five dose levels, with at least three patients entered at each dose level. RESULTS Clear tumor images were observed in 12 patients with G250-positive tumors and in one of three patients with G250-negative tumors. Imaged lesions in the peritoneal cavity were confirmed at surgery. The smallest lesion visualized was 8 mm in diameter. The specificity of 131I-mAbG250 localization to tumor tissue was established by radioactivity measurements, autoradiography, and immunohistochemistry of biopsied tissues, and technetium 99-human serum albumin blood-flow studies. The fraction of the injected 131I-mAbG250 dose per gram tumor (%ID/g tumor) localized in G250-positive tumors showed a broad range, but reached levels as high as 0.02% to 0.12%. CONCLUSION 131I-mAbG250 localized specifically to G250 antigen-positive RCC and seems to have considerable potential as an imaging agent in RCC patients. 131I-mAbG250 uptake in the tumors, relative as well as absolute, are among the highest reported for tumor biopsies obtained 8 days after IV mAb administration. Based on the specific localization and high accumulation, mAb G250 may have therapeutic potential.

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