更新于：2024-05-14
SIM-323
更新于：2024-05-14
概要
基本信息
药物类型 融合蛋白 |
别名 bi-specific fragment crystallizable region (Fc) fusion protein containing cluster of differentiation 80 ectodomain as an N-terminal moiety and interleukin-2 variant as a C-terminal moiety conjugated with human immunoglobulin G4 Fc、GI 101、GI-101 + [1] |
作用机制 CD28抑制剂(T细胞特异性表面糖蛋白CD28抑制剂)、CTLA4抑制剂(细胞毒性T淋巴细胞相关抗原4抑制剂)、IL-2R调节剂(白细胞介素-2受体复合体调节剂) |
非在研适应症- |
非在研机构 |
最高研发阶段临床1/2期 |
首次获批日期- |
最高研发阶段(中国)无进展 |
特殊审评孤儿药 (美国) |
序列信息
Sequence Code 5063
靶点: *****
Sequence Code 6077linker
Sequence Code 315647156
Sequence Code 524284409linker
Sequence Code 524284410
Sequence Code 524284411
Sequence Code 524284413Fusion protein
关联
1
项与 SIM-323 相关的临床试验A Phase 1/2, Open-label, Dose-escalation, and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Therapeutic Activity of GI-101 as a Single Agent and in Combination With Pembrolizumab, Lenvatinib or Local Radiotherapy in Patients With Advanced or Metastatic Solid Tumors (Keynote B59)
100 项与 SIM-323 相关的临床结果
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100 项与 SIM-323 相关的转化医学
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100 项与 SIM-323 相关的专利（医药）
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3
项与 SIM-323 相关的文献（医药）2010-08-01Breast cancer research : BCR1区 · 医学
Association of invasion-promoting tenascin-C additional domains with breast cancers in young women
1区 · 医学
ArticleOA
作者: Rachael A Hancox ; Rosemary A Walker ; J Howard Pringle ; Jacqueline A Shaw ; David S Guttery ; J Louise Jones ; Kellie T Mulligan ; Sinead M Lambe ; Simon Hughes
INTRODUCTION:
Tenascin-C (TNC) is a large extracellular matrix glycoprotein that shows prominent stromal expression in many solid tumours. The profile of isoforms expressed differs between cancers and normal breast, with the two additional domains AD1 and AD2 considered to be tumour associated. The aim of the present study was to investigate expression of AD1 and AD2 in normal, benign and malignant breast tissue to determine their relationship with tumour characteristics and to perform in vitro functional assays to investigate the role of AD1 in tumour cell invasion and growth.
METHODS:
Expression of AD1 and AD2 was related to hypoxanthine phosphoribosyltransferase 1 as a housekeeping gene in breast tissue using quantitative RT-PCR, and the results were related to clinicopathological features of the tumours. Constructs overexpressing an AD1-containing isoform (TNC-14/AD1/16) were transiently transfected into breast carcinoma cell lines (MCF-7, T-47 D, ZR-75-1, MDA-MB-231 and GI-101) to assess the effect in vitro on invasion and growth. Statistical analysis was performed using a nonparametric Mann-Whitney test for comparison of clinicopathological features with levels of TNC expression and using Jonckheere-Terpstra trend analysis for association of expression with tumour grade.
RESULTS:
Quantitative RT-PCR detected AD1 and AD2 mRNA expression in 34.9% and 23.1% of 134 invasive breast carcinomas, respectively. AD1 mRNA was localised by in situ hybridisation to tumour epithelial cells, and more predominantly to myoepithelium around associated normal breast ducts. Although not tumour specific, AD1 and AD2 expression was significantly more frequent in carcinomas in younger women (age ≤40 years; P < 0.001) and AD1 expression was also associated with oestrogen receptor-negative and grade 3 tumours (P < 0.05). AD1 was found to be incorporated into a tumour-specific isoform, not detected in normal tissues. Overexpression of the TNC-14/AD1/16 isoform significantly enhanced tumour cell invasion (P < 0.01) and growth (P < 0.01) over base levels.
CONCLUSIONS:
Together these data suggest a highly significant association between AD-containing TNC isoforms and breast cancers in younger women (age ≤40 years), which may have important functional significance in vivo.
1997-01-01The international journal of biochemistry & cell biology2区 · 生物学
Expression of connective tissue growth factor mRNA in the fibrous stroma of mammary tumors
2区 · 生物学
Article
作者: Gary R. Grotendorst ; Ken S. Frazier
Desmoplasia, the formation of highly cellular, excessive connective tissue stroma associated with some cancers, shares many features with the wound healing response. Since connective tissue growth factor (CTGF) has previously been demonstrated to play a role in wound repair, we wanted to determine if it might be involved in the pathogenesis of stromal demoplasia in mammary cancer. We assayed 11 human invasive mammary ductal carcinomas by Northern blot and 7 out of 11 were positive for both CTGF expression and transforming growth factor-beta 1 (TGF-beta 1, a principal CTGF inducer). One specimen was positive only for TGF-beta 1. The remaining 3 tumors lacked significant stromal involvement and were negative for either factor. In every case we assayed, in which there was marked connective tissue involvement, both CTGF and TGF-beta 1 messages were found. We also assayed 3 murine mammary tumor models. The GI-101 xenograft model had marked stroma and was positive for both factors in-vivo, but positive for only TGF-beta 1 mRNA expression in culture where fibroblasts were absent. The DMBA murine tumor lacked significant stroma and was negative for CTGF and TGF-beta 1 expression by Northern blot, while the stromal rich DMBA-MMTV tumor contained multifocal desmoplasia and was positive for both factors. We performed in-situ hybridization for CTGF and TGF-beta 1 on the GI-101 and DMBA-MMTV tumors. CTGF message was observed only in the fibroblasts of the stroma, while TGF-beta 1 mRNA hybridization was present in tumor epithelial cells and leukocytes. These results suggest that cancer stroma formation involves induction of similar fibroproliferative growth factors (TGF-beta 1 and CTGF) as wound repair.
1993-08-01British journal of cancer1区 · 医学
A novel model of a metastatic human breast tumour xenograft line
1区 · 医学
Article
作者: Tombarkiewicz, J ; Hurst, J ; Perras, J ; Roberson, C ; James, W ; Lucas, F ; Maniar, N ; Steplewski, Z
The GI-101 human breast tumour xenograft line is unique in that it spontaneously metastasizes to the lungs of athymic murine hosts from subcutaneous trochar implants. Both tumour and lung metastases are positive for normal human breast tissue markers. GI-101 also is positive for the p53 antigen but negative for the c-erbB-2 oncogene.
1
项与 SIM-323 相关的新闻（医药）2022-08-23
合作抗体基因疗法生物类似药First in Class
100 项与 SIM-323 相关的药物交易
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研发状态
| 适应症 | 最高研发状态 | 国家/地区 | 公司 |
|---|---|---|---|
| 晚期恶性实体瘤 | 临床2期 | 韩国 更多 | |
| 非小细胞肺癌 | 临床2期 | 美国 更多 | |
| 阴道肿瘤 | 临床2期 | 美国 更多 | |
| 外阴肿瘤 | 临床2期 | 美国 更多 | |
| 实体瘤 | 无进展 | 中国 更多 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床1/2期 | 57 | 鑰齋蓋鑰艱鹽築淵築築(窪選醖鏇願壓襯廠淵鏇) = 糧積衊鬱蓋壓範簾夢餘 糧鑰簾範網糧簾顧鑰遞 (膚鏇廠鏇鹽鹽糧糧蓋範 ) 更多 | 积极 | 2023-10-23 | |||
(MSS CRC with liver metastasis) | 餘壓製憲構壓範鹹獵夢(糧遞鏇廠範獵襯餘鬱鹹) = 襯遞選廠蓋鹽憲範築醖 鹹積範遞觸壓願願顧獵 (網遞範選願壓遞築觸鏇 ) | ||||||
临床1/2期 | 25 | 糧鹹衊壓遞願築網選築(鹽膚願遞範衊蓋顧夢壓) = No dose-limiting toxicities up to 0.15 mg/kg were reported with planned dose level of 0.002~0.6 mg/kg. 繭鹽齋憲艱積遞範膚構 (壓窪醖築願憲觸齋齋繭 ) | 积极 | 2022-11-01 | |||
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