A Dose Escalation Study to Evaluate Safety, Tolerability Dosimetry, Pharmacokinetics and Preliminary Efficacy of 131I-Tenatumomab Treatment in Tenascin-C Positive Cancer Patients

Tenatumomab is a Sigma-Tau developed new anti-Tenascin antibody. It is a murine monoclonal antibody directed towards Tenascin-C. By means of this antibody, Tenascin-C expression was studied on a commercial tissue array slides each carrying malignant breast, colorectal, lung, ovarian or B and T cell Non-Hodgkin Limphoma tissue sections. All these cancers type showed positivity to Tenascin-C between the 64% and 13.3%. Consequently, Sigma-tau is exploring the use of the 131I-labeled Tenatumomab for anti-cancer radioimmunotherapy.

开始日期2015-11-01

申办/合作机构

Sigma Tau I.f.r S.p.a.

[+1]

100 项与 131 Iodine-Tenatumomab 相关的临床结果

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100 项与 131 Iodine-Tenatumomab 相关的转化医学

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100 项与 131 Iodine-Tenatumomab 相关的专利（医药）

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项与 131 Iodine-Tenatumomab 相关的文献（医药）

2024-01-01·Pharmacology & Therapeutics

Clinical advances in TNC delivery vectors and their conjugate agents

Review

作者: Wang, Chao ; Liang, Bing ; Jiang, Hongfei ; Shen, Xin ; Wang, Shuai ; Wu, Yudong ; Liu, Xinlin ; Xing, Xiaohui ; Chen, Wujun ; Wang, Jie ; Xing, Dongming ; Yu, Wanpeng ; Zhao, Kai ; Zhang, Miao ; Hu, Xiaokun

Tenascin C (TNC), a glycoprotein that is abundant in the tumor extracellular matrix (ECM), is strongly overexpressed in tumor tissues but virtually undetectable in most normal tissues. Many TNC antibodies, peptides, aptamers, and nanobodies have been investigated as delivery vectors, including 20A1, α-A2, α-A3, α-IIIB, α-D, BC-2, BC-4 BC-8, 81C6, ch81C6, F16, FHK, Ft, Ft-NP, G11, G11-iRGD, GBI-10, 19H12, J1/TN1, J1/TN2, J1/TN3, J1/TN4, J1/TN5, NJT3, NJT4, NJT6, P12, PL1, PL3, R6N, SMART, ST2146, ST2485, TN11, TN12, TNFnA1A2-Fc, TNfnA1D-Fc, TNfnBD-Fc, TNFnCD-Fc, TNfnD6-Fc, TNfn78-Fc, TTA1, TTA1.1, and TTA1.2. In particular, BC-2, BC-4, 81C6, ch81C6, F16, FHK, G11, PL1, PL3, R6N, ST2146, TN11, and TN12 have been tested in human tissues. G11-iRGD and simultaneous multiple aptamers and arginine-glycine-aspartic acid (RGD) targeting (SMART) may be assessed in clinical trials because G11, iRGD and AS1411 (SMART components) are already in clinical trials. Many TNC-conjugate agents, including antibody-drug conjugates (ADCs), antibody fragment-drug conjugates (FDCs), immune-stimulating antibody conjugates (ISACs), and radionuclide-drug conjugates (RDCs), have been investigated in preclinical and clinical trials. RDCs investigated in clinical trials include ¹¹¹In-DTPA-BC-2, ¹³¹I-BC-2, ¹³¹I-BC-4, ⁹⁰Y-BC4, ¹³¹I81C6, ¹³¹I-ch81C6, ²¹¹At-ch81C6, F16¹²⁴I, ¹³¹I-tenatumomab, ST2146biot, FDC ¹³¹I-F16S1PF(ab')2, and ISAC F16IL2. ADCs (including FHK-SSL-Nav, FHK-NB-DOX, Ft-NP-PTX, and F16*-MMAE) and ISACs (IL12-R6N and ¹²⁵I-G11-IL2) may enter clinical trials because they contain components of marketed treatments or agents that were investigated in previous clinical studies. This comprehensive review presents historical perspectives on clinical advances in TNC-conjugate agents to provide timely information to facilitate tumor-targeting drug development using TNC.

2019-06-01·Acta Neurochirurgica3区 · 医学

Intracavitary radioimmunotherapy of high-grade gliomas: present status and future developments

3区 · 医学

Review

作者: Reulen, Hans-Jürgen ; Gildehaus, Franz Josef ; Suero Molina, Eric ; Stummer, Walter ; Gosewisch, Astrid ; Zeidler, Reinhard ; Böning, Guido

There is a distinct need for new and second-line therapies to delay or prevent local tumor regrowth after current standard of care therapy. Intracavitary radioimmunotherapy, in combination with radiotherapy, is discussed in the present review as a therapeutic strategy of high potential. We performed a systematic literature search following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The available body of literature on intracavitary radioimmunotherapy (iRIT) in glioblastoma and anaplastic astrocytomas is presented. Several past and current phase I and II clinical trials, using mostly an anti-tenascin monoclonal antibody labeled with I-131, have shown median overall survival of 19-25 months in glioblastoma, while adverse events remain low. Tenascin, followed by EGFR and variants, or smaller peptides have been used as targets, and most clinical studies were performed with I-131 or Y-90 as radionuclides while only recently Re-188, I-125, and Bi-213 were applied. The pharmacokinetics of iRIT, as well as the challenges encountered with this therapy, is comprehensively discussed. This promising approach deserves further exploration in future studies by incorporating several innovative modifications.

1999-09-01·Bioconjugate Chemistry2区 · 化学

Preparation and Characterization of Anti-Tenascin Monoclonal Antibody−Streptavidin Conjugates for Pretargeting Applications

2区 · 化学

Article

作者: Bigner, Darell D. ; Zalutsky, Michael R. ; Foulon, Catherine F.

Radioimmunopretargeting is based on the separate injection of a modified mAb and the radionuclide and most frequently exploits the very high avidity of biotin for streptavidin (SA). Currently, we are evaluating the therapeutic potential of directly labeled monoclonal antibody (mAb) 81C6, reactive with the extracellular matrix protein tenascin, in surgically created glioma resection cavity patients. To be able to investigate pretargeting in this setting, the synthesis of 81C6 mAb-SA conjugates was required. In the current study, we have evaluated five methods for preparing both murine 81C6 (m81C6) and human/mouse chimeric 81C6 (c81C6) SA conjugates with regard to yield, biotin-binding capacity, immunoreactivity, and molecular weight. The 81C6 mAb and SA were coupled by covalent interaction between sulfhydryl groups generated on the mAb via N-succinimidyl-S-acetylthioacetate, dithiothreitol or 2-iminothiolane (2IT), and maleimido-derivatized SA, prepared via sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) or N-succinimidyl-3-(2-pyridyldithio)-propionate. A noncovalent approach involving reaction of a biotinylated mAb, prepared using biotin caproate, and SA also was studied. The evaluation criteria were yield of mAb-SA 215 kDa monomer, as well as conjugate biotin-binding capacity and immunoreactive fraction. The optimal procedure involved activation of m81C6 or c81C6 with 30 equiv of 2IT and reaction of SA with 10 equiv of SMCC and yielded a conjugate with excellent biotin-binding capacity and immunoreactivity. The ((125)I-labeled m81C6)-2IT-SMCC-SA was stable and did not lose biotin-binding capacity after a 72 h incubation in human glioma cyst fluid in vitro. Although the conjugate was stable in murine serum in vivo, its biotin-binding capacity declined rapidly, consistent with high endogenous biotin levels in the mouse. After injection of the radioiodinated conjugate into athymic mice with subcutaneous D-54 MG human glioma xenografts, high tumor uptake (36.0 +/- 10.7% ID/g at 3 days) and excellent tumor:normal tissue ratios were observed.

100 项与 131 Iodine-Tenatumomab 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
结缔组织和软组织肿瘤	临床2期	意大利	Alfasigma SpA	2015-11-01
结缔组织和软组织肿瘤	临床2期	意大利	Sigma Tau I.f.r S.p.a.	2015-11-01
结缔组织和软组织肿瘤	临床2期	法国	Sigma Tau I.f.r S.p.a.	2015-11-01
泌尿生殖系统肿瘤	临床2期	意大利	Alfasigma SpA	2015-11-01
泌尿生殖系统肿瘤	临床2期	意大利	Sigma Tau I.f.r S.p.a.	2015-11-01
泌尿生殖系统肿瘤	临床2期	法国	Alfasigma SpA	2015-11-01
泌尿生殖系统肿瘤	临床2期	法国	Sigma Tau I.f.r S.p.a.	2015-11-01
血液肿瘤	临床1期	-	Sigma-Tau BV	-
肿瘤	临床1期	意大利	Sigma-Tau Industrie Farmaceutiche Riunite SpA	-
肿瘤	临床1期	法国	Sigma-Tau Industrie Farmaceutiche Riunite SpA	-