Last update 01 Nov 2024

MMP2 positive Glioblastoma

Last update 01 Nov 2024

Basic Info

Synonyms-

Introduction-

Drugs associated with MMP2 positive Glioblastoma

CHM-1101

Target

CD19 x CD28 x CD3

Mechanism

CD19 inhibitors [+2]

Active Org.

City of Hope National Medical Center [+2]

Originator Org.

City of Hope National Medical Center

Active Indication

Glioblastoma Multiforme [+7]

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with MMP2 positive Glioblastoma

NCT05627323 / Active, not recruitingPhase 1

A Phase 1b Study to Evaluate CHM-1101, a CAR T-Cell Therapy With a Chlorotoxin Tumor-Targeting Domain for Patients With Matrix Metallopeptidase 2 Positive (MMP2+) Recurrent or Progressive Glioblastoma Multiforme

This is a phase 1b study to evaluate the safety of chimeric antigen receptor (CAR) T cells with a chlorotoxin tumor-targeting domain (ie, CHM-1101, the study treatment) to determine the best dose of CHM-1101, and to assess the effectiveness of CHM-1101 in treating MMP2+ glioblastoma that has come back (recurrent) or that is growing, spreading, or getting worse (progressive).

Start Date06 Jun 2023

Sponsor / Collaborator

Chimeric Therapeutics Ltd.

NCT04214392 / RecruitingPhase 1IIT

A Phase 1 Study to Evaluate Chimeric Antigen Receptor (CAR) T Cells With a Chlorotoxin Tumor-Targeting Domain for Patients With MMP2+ Recurrent or Progressive Glioblastoma

This phase I trial studies the side effects and best dose of chimeric antigen receptor (CAR) T cells with a chlorotoxin tumor-targeting domain in treating patients with MPP2+ glioblastoma that has come back (recurrent) or that is growing, spreading, or getting worse (progressive). Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells.

Start Date26 Feb 2020

Sponsor / Collaborator

City of Hope National Medical Center

[+1]

100 Clinical Results associated with MMP2 positive Glioblastoma

100 Translational Medicine associated with MMP2 positive Glioblastoma

0 Patents (Medical) associated with MMP2 positive Glioblastoma

Literatures (Medical) associated with MMP2 positive Glioblastoma

17 Nov 2018·Nutrition and CancerQ4 · MEDICINE

Epigallocatechin Gallate Preferentially Inhibits O⁶-Methylguanine DNA-Methyltransferase Expression in Glioblastoma Cells Rather than in Nontumor Glial Cells

Q4 · MEDICINE

Article

Author: Zhang, Nu ; You, Chao-Guo ; Sheng, Han-Song ; Zheng, Xue-Sheng ; Xie, Chao-Ran

OBJECTIVEO⁶-methylguanine (O6-meG) DNA-methyltransferase (MGMT) is a main regulator of temozolomide (TMZ) resistance in glioblastomas. Some MGMT inhibitors have been studied in clinical trials but with very little success, because their inhibiting effects were not tumor-selective, and often cause severe toxicity in normal tissues in the presence of TMZ. The goal of this study is to explore whether Epigallocatechin gallate (EGCG), a natural small molecule, could preferentially modulate MGMT in glioblastoma cells.METHODSTwo MGMT-positive glioblastoma cell lines (GBM-XD and T98G) and one nontumor glial cell culture (GliaX) were included in this study. The MGMT promoter methylation status, mRNA abundance, and protein levels were determined before and after EGCG treatment. The mechanisms were characterized.RESULTSEGCG substantially suppressed mRNA and protein expression of MGMT, and reversed TMZ resistance in MGMT-positive GBM-XD and T98G cells via the WNT/β-catenin pathway. EGCG prevented β-catenin translocation into the nucleus and might directly inhibit the transcription factors TCF1 and LEF1. Meanwhile, EGCG enhanced the MGMT expression in the nontumor glial cells, through inhibition of the DNMT1 and demethylation of MGMT promoter.CONCLUSIONSEGCG preferentially inhibits MGMT and enhances TMZ cytotoxicity in glioblastoma cells rather than in nontumor glial cells.

01 Oct 2016·Journal of the Chinese Medical AssociationQ4 · MEDICINE

Sox2, a stemness gene, regulates tumor-initiating and drug-resistant properties in CD133-positive glioblastoma stem cells

Q4 · MEDICINE

Article

Author: Pin-I Huang ; Yi-Yen Lee ; Yi-Wei Chen ; Wai-Wah Wu ; Ming-Teh Chen ; Yi-Ping Yang ; Chi-Shuan Huang ; Wen-Shin Song ; Shou-Dong Lee ; Wei-Hsiu Liu ; Wen-Liang Lo ; Kai-Hsi Lu

BACKGROUNDGlioblastoma multiforme (GBM) is the most lethal type of adult brain cancer and performs outrageous growth and resistance regardless of adjuvant chemotherapies, eventually contributing to tumor recurrence and poor outcomes. Considering the common heterogeneity of cancer cells, the imbalanced regulatory mechanism could be switched on/off and contribute to drug resistance. Moreover, the subpopulation of GBM cells was recently discovered to share similar phenotypes with neural stem cells. These cancer stem cells (CSCs) promote the potency of tumor initiation. As a result, targeting of glioma stem cells has become the dominant way of improving the therapeutic outcome against GBM and extending the life span of patients. Among the biomarkers of CSCs, CD-133 (prominin-1) has been known to effectively isolate CSCs from cancer population, including GBM; however, the underlying mechanism of how stemness genes manipulate CSC-associated phenotypes, such as tumor initiation and relapse, is still unclear.METHODSTumorigenicity, drug resistance and embryonic stem cell markers were examined in primary CD133-positive (CD133(+)) GBM cells and CD133(+) subpopulation. Stemness signature of CD133(+) GBM cells was identified using microarray analysis. Stem cell potency, tumorigenicity and drug resistance were also tested in differential expression of SOX2 in GBM cells.RESULTSIn this study, high tumorigenic and drug resistance was noticed in primary CD-133(+) GBM cells; meanwhile, plenty of embryonic stem cell markers were also elevated in the CD-133+ subpopulation. Using microarray analysis, we identified SOX2 as the most enriched gene among the stemness signature in CD133(+) GBM cells. Overexpression of SOX2 consistently enhanced the stem cell potency in the GBM cell lines, whereas knockdown of SOX2 dramatically withdrew CD133 expression in CD133(+) GBM cells. Additionally, we silenced SOX2 expression using RNAi system, which abrogated the ability of tumor initiation as well as drug resistance of CD133(+) GBM cells, suggesting that SOX2 plays a crucial role in regulating tumorigenicity in CD133(+) GBM cells.CONCLUSIONSOX2 plays a crucial role in regulating tumorigenicity in CD133(+) GBM cells. Our results not only revealed the genetic plasticity contributing to drug resistance and stemness but also demonstrated the dominant role of SOX2 in maintenance of GBM CSCs, which may provide a novel therapeutic target to overcome the conundrum of poor survival of brain cancers.

09 Sep 2015·ACS Applied Materials & InterfacesQ2 · MATERIALS SCIENCE

Chlorotoxin-Conjugated Multifunctional Dendrimers Labeled with Radionuclide ¹³¹I for Single Photon Emission Computed Tomography Imaging and Radiotherapy of Gliomas

Q2 · MATERIALS SCIENCE

Article

Author: Zhao, Jinhua ; Guo, Lilei ; Zhu, Jingyi ; Cheng, Yongjun ; Zhao, Lingzhou ; Shi, Xiangyang ; Tang, Yueqin ; Xiong, Zhijuan

Chlorotoxin-conjugated multifunctional dendrimers labeled with radionuclide 131I were synthesized and utilized for targeted single photon emission computed tomography (SPECT) imaging and radiotherapy of cancer. In this study, generation five amine-terminated poly(amidoamine) dendrimers were used as a platform to be sequentially conjugated with polyethylene glycol (PEG), targeting agent chlorotoxin (CTX), and 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO). This was followed by acetylation of the remaining dendrimer terminal amines and radiolabeling with 131I to form the targeted theranostic dendrimeric nanoplatform. We show that the dendrimer platform possessing approximately 7.7 CTX and 21.1 HPAO moieties on each dendrimer displays excellent cytocompatibility in a given concentration range (0-20 μM) and can specifically target cancer cells overexpressing matrix metallopeptidase 2 (MMP2) due to the attached CTX. With the attached HPAO moiety having the phenol group, the dendrimer platform can be effectively labeled with radioactive 131I with good stability and high radiochemical purity. Importantly, the 131I labeling renders the dendrimer platform with an ability to be used for targeted SPECT imaging and radiotherapy of an MMP2-overexpressing glioma model in vivo. The developed radiolabeled multifunctional dendrimeric nanoplatform may hold great promise to be used for targeted theranostics of human gliomas.

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MMP2 positive Glioblastoma

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