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概览

疾病领域	数量

肿瘤	3
血液及淋巴系统疾病	1
免疫系统疾病	1

排名前五的药物类型	数量

ADC	3
诊断用放射药物	1
抗体偶联核素	1

排名前五的靶点	数量

HER2(受体蛋白酪氨酸激酶 erbB-2)	1

关联

7

项与 Avipep Pty Ltd. 相关的药物

Iodine-124-AVP-0458

靶点-

作用机制

PET imaging

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段临床阶段不明

首次获批国家/地区-

首次获批日期-

Anti-HER2 single-chain Fv dimer-deBouganin ADC(Sesen Bio/AviPep)

靶点

HER2

作用机制

HER2拮抗剂

在研机构

Avipep Pty Ltd. [+1]

原研机构

Viventia Bio, Inc.

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

AVP10

靶点-

作用机制-

在研机构

Avipep Pty Ltd.

原研机构

Avipep Pty Ltd.

在研适应症

间变性大细胞淋巴瘤 [+2]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

1

项与 Avipep Pty Ltd. 相关的临床试验

ACTRN12612000802808 / Completed临床1期

Phase I Safety and Biodistribution Study of 124I-PEG-AVP0458 Diabody in Patients with TAG-72 Positive Ovarian and Prostate Cancer

开始日期2012-08-29

申办/合作机构

Avipep Pty Ltd.

100 项与 Avipep Pty Ltd. 相关的临床结果

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0 项与 Avipep Pty Ltd. 相关的专利（医药）

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6

项与 Avipep Pty Ltd. 相关的文献（医药）

2021-03-01·Molecular Therapy - Oncolytics2区 · 医学

Engineered CAR-T cells targeting TAG-72 and CD47 in ovarian cancer

2区 · 医学

ArticleOA

作者: Evtimov, Vera J ; Howard, Maureen C ; Trounson, Alan O ; Pupovac, Aleta ; Hammett, Maree V ; Zhuang, Junli ; Hudson, Peter J ; Nguyen, Nhu-Y N ; Boyd, Richard L ; Shu, Runzhe

Chimeric antigen receptor (CAR) T cells have revolutionized blood cancer immunotherapy; however, their efficacy against solid tumors has been limited. A common mechanism of tumor escape from single target therapies is downregulation or mutational loss of the nominal epitope. Targeting multiple antigens may thus improve the effectiveness of CAR immunotherapies. We generated dual CAR-T cells targeting two tumor antigens: TAG-72 (tumor-associated glycoprotein 72) and CD47. TAG-72 is a pan-adenocarcinoma oncofetal antigen, highly expressed in ovarian cancers, with increased expression linked to disease progression. CD47 is ubiquitously overexpressed in multiple tumor types, including ovarian cancer; it is a macrophage "don't eat me" signal. However, CD47 is also expressed on many normal cells. To avoid this component of the dual CAR-T cells killing healthy tissue, we designed a truncated CD47 CAR devoid of intracellular signaling domains. The CD47 CAR facilitates binding to CD47⁺ cells, increasing the prospect of TAG-72⁺ cell elimination via the TAG-72 CAR. Furthermore, we could reduce the damage to normal tissue by monomerizing the CD47 CAR. Our results indicate that the co-expression of the TAG-72 CAR and the CD47-truncated monomer CAR on T cells could be an effective, dual CAR-T cell strategy for ovarian cancer, also applicable to other adenocarcinomas.

2016-07-15·Cancer Research

Abstract 2963: VB7-756: a Her2-specific diabody armed with deBouganin, a plant toxin with a distinct MOA

作者: Chooniedass, Shilpa ; Entwistle, Joycelyn ; Dillon, Rachelle L. ; Premsukh, Arjune ; Cizeau, Jeannick ; MacDonald, Glen C. ; Adams, Gregory P. ; Hudson, Peter J.

AbstractVB7-756 is Targeted Protein Therapeutic (TPT) comprised of a de-immunized form of bouganin (deBouganin), a potent, plant-derived, type I ribosome-inactivating protein (RIP), genetically linked to the C6.5 anti-Her2 diabody via a furin protease sensitive linker. To engineer the optimal diabody TPT format, several constructs were generated to assess the best diabody-deBouganin orientation. All constructs were expressed as a soluble protein in E. coli supernatant and compared with respect to expression level, stability and potency. The optimal configuration consisted of deBouganin genetically linked to the N-terminus of the VH-VL diabody via a furin protease-sensitive linker and was termed VB7-756. VB7-756 potency was analyzed against a panel of breast cancer cell lines with disparate levels of Her-2 expression and compared to that of Trastuzumab chemically linked to either DM1 (T-DM1) or MMAE (T-MMAE). Overall, VB7-756 was more potent than T-DM1 and T-MMAE with high Her-2 expressing tumor cell lines. In contrast to T-DM1, VB7-756 potency was unaffected by the Her2-Her3 dimerization mediated by heregulin. As opposed to T-DM1 and T-MMAE, which showed only minimal cytoxicity, VB7-756 was highly potent in vitro against tumor cells with cancer stem cell properties. To further differentiate the RIP mechanism of action of deBouganin from tubulin inhibitor reagents, tumor cells that escaped T-DM1 and T-MMAE treatment were incubated in the presence of VB7-756. Results revealed that, VB7-756 was cytotoxic against cancer cells surviving T-DM1 or T-MMAE treatment suggesting that deBouganin can overcome mechanisms of resistance developed by small molecule agents. Moreover, VB7-756 was also cytotoxic against tumor initiating cancer cells evading T-DM1 or T-MMAE toxicity by preventing tumorosphere formation. Overall these results demonstrate that deBouganin's distinct MOA could overcome mechanisms of resistance affecting the efficacy of small molecule drugs.Citation Format: Shilpa Chooniedass, Rachelle L. Dillon, Arjune Premsukh, Joycelyn Entwistle, Gregory P. Adams, Peter J. Hudson, Glen C. MacDonald, Jeannick Cizeau. VB7-756: a Her2-specific diabody armed with deBouganin, a plant toxin with a distinct MOA. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2963.

2015-09-01·Journal of Nuclear Medicine1区 · 医学

Diabody Pretargeting with Click Chemistry In Vivo

1区 · 医学

Article

作者: Robillard, Marc S ; Wheatcroft, Michael P ; van den Bosch, Sandra M ; Hudson, Peter J ; Rossin, Raffaella ; van Duijnhoven, Sander M J

Radioimmunotherapy and nuclear imaging (immuno-PET/SPECT) of cancer with radiometal-labeled antibody fragments or peptides is hampered by low tumor-to-kidney ratios because of high renal radiometal retention. Therefore, we developed and evaluated a pretargeting strategy using click chemistry in vivo to reduce kidney uptake and avoid unwanted radiation toxicity. We focused on the bioorthogonal reaction between a trans-cyclooctene (TCO)-functionalized TAG72 targeting diabody, AVP04-07, and a low-molecular-weight radiolabeled tetrazine probe that was previously shown to have low kidney retention and relatively fast renal clearance.METHODSAVP04-07 diabodies were functionalized with TCO tags, and in vitro immunoreactivity toward bovine submaxillary mucin and tetrazine reactivity were assessed. Next, pretargeting biodistribution studies were performed in LS174T tumor-bearing mice with AVP04-07-TCO(n) (where n indicates the number of TCO groups per diabody) and radiolabeled tetrazine to optimize the TCO modification grade (0, 1.8, or 4.7 TCO groups per diabody) and the (177)Lu-tetrazine dose (0.1, 1.0, or 10 Eq with respect to the diabody). Radiolabeled tetrazine was injected at 47 h after diabody injection, and mice were euthanized 3 h later. A pretargeting SPECT/CT study with (111)In-tetrazine was performed with the optimized conditions.RESULTSImmunoreactivity for native AVP04-07 was similar to that for TCO-functionalized AVP04-07, and the latter reacted efficiently with radiolabeled tetrazine in vitro. The combination of the pretargeting component AVP04-07 functionalized with 4.7 TCO groups and 1 Eq of (177)Lu-tetrazine with respect to the diabody showed the most promising biodistribution. Specifically, high (177)Lu-tetrazine tumor uptake (6.9 percentage injected dose/g) was observed with low renal retention, yielding a tumor-to-kidney ratio of 5.7. SPECT/CT imaging confirmed the predominant accumulation of radiolabeled tetrazine in the tumor and low nontumor retention.CONCLUSIONPretargeting provides an alternative radioimmunotherapy and nuclear imaging strategy by overcoming the high renal retention of low-molecular-weight radiometal tumor-homing agents through the separate administration of a tumor-homing agent and a radioactive probe with fast clearance.

100 项与 Avipep Pty Ltd. 相关的药物交易

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100 项与 Avipep Pty Ltd. 相关的转化医学

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管线布局中药物为当前组织机构及其子机构作为药物机构进行统计，早期临床1期并入临床1期，临床1/2期并入临床2期，临床2/3期并入临床3期

临床前

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当前项目

药物(靶点)	适应症	全球最高研发状态

Iodine-124-AVP-0458	腺癌更多	临床阶段不明
AVP20	-	临床前
AVP10	间变性大细胞淋巴瘤更多	临床前
Anti-HER2 single-chain Fv dimer-deBouganin ADC(Sesen Bio/AviPep) ( HER2 )	肿瘤更多	临床前
ADC-AVP-04(Avipep)	胃癌更多	终止