A peptide–doxorubicin 'prodrug' activated by prostate-specific antigen selectively kills prostate tumor cells positive for prostate-specific antigen in vivo

10.1038/81351 ◽  
2000 ◽  
Vol 6 (11) ◽  
pp. 1248-1252 ◽  
Author(s):  
Deborah DeFeo-Jones ◽  
Victor M. Garsky ◽  
Bradley K. Wong ◽  
Dong-Mei Feng ◽  
Trina Bolyar ◽  
...  
Keyword(s):  
Prostate Specific Antigen ◽  
Tumor Cells ◽  
Specific Antigen ◽  
Prostate Tumor ◽  
Prostate Tumor Cells

scholarly journals Adenovirus E2F1 Overexpression Sensitizes LNCaP and PC3 Prostate Tumor Cells to Radiation In Vivo

2011 ◽  
Vol 79 (2) ◽  
pp. 549-558 ◽  
Author(s):  
Thirupandiyur S. Udayakumar ◽  
Radka Stoyanova ◽  
Paul Hachem ◽  
Mansoor M. Ahmed ◽  
Alan Pollack
Keyword(s):  
Tumor Cells ◽  
Prostate Tumor ◽  
Prostate Tumor Cells

scholarly journals Attenuating CD3 affinity in a PSMAxCD3 bispecific antibody enables killing of prostate tumor cells with reduced cytokine release

2021 ◽  
Vol 9 (6) ◽  
pp. e002488
Author(s):  
Kevin Dang ◽  
Giulia Castello ◽  
Starlynn C Clarke ◽  
Yuping Li ◽  
Aarti Balasubramani ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Prostate Tumor ◽  
Cytokine Release ◽  
High Affinity ◽  
Prostate Tumor Cells ◽  
3D Spheroids

BackgroundTherapeutic options currently available for metastatic castration-resistant prostate cancer (mCRPC) do not extend median overall survival >6 months. Therefore, the development of novel and effective therapies for mCRPC represents an urgent medical need. T cell engagers (TCEs) have emerged as a promising approach for the treatment of mCRPC due to their targeted mechanism of action. However, challenges remain in the clinic due to the limited efficacy of TCEs observed thus far in solid tumors as well as the toxicities associated with cytokine release syndrome (CRS) due to the usage of high-affinity anti-CD3 moieties such as OKT3.MethodsUsing genetically engineered transgenic rats (UniRat and OmniFlic) that express fully human IgG antibodies together with an NGS-based antibody discovery pipeline, we developed TNB-585, an anti-CD3xPSMA TCE for the treatment of mCRPC. TNB-585 pairs a tumor-targeting anti-PSMA arm together with a unique, low-affinity anti-CD3 arm in bispecific format. We tested TNB-585 in T cell-redirected cytotoxicity assays against PSMA+ tumor cells in both two-dimensional (2D) cultures and three-dimensional (3D) spheroids as well as against patient-derived prostate tumor cells. Cytokines were measured in culture supernatants to assess the ability of TNB-585 to induce tumor killing with low cytokine release. TNB-585-mediated T cell activation, proliferation, and cytotoxic granule formation were measured to investigate the mechanism of action. Additionally, TNB-585 efficacy was evaluated in vivo against C4-2 tumor-bearing NCG mice.ResultsIn vitro, TNB-585 induced activation and proliferation of human T cells resulting in the killing of PSMA+ prostate tumor cells in both 2D cultures and 3D spheroids with minimal cytokine release and reduced regulatory T cell activation compared with a positive control antibody that contains the same anti-PSMA arm but a higher affinity anti-CD3 arm (comparable with OKT3). In addition, TNB-585 demonstrated potent efficacy against patient-derived prostate tumors ex vivo and induced immune cell infiltration and dose-dependent tumor regression in vivo.ConclusionsOur data suggest that TNB-585, with its low-affinity anti-CD3, may be efficacious while inducing a lower incidence and severity of CRS in patients with prostate cancer compared with TCEs that incorporate high-affinity anti-CD3 domains.

Myosin II heavy chain isoforms are phosphorylated in an EGF-dependent manner

2001 ◽  
Vol 114 (16) ◽  
pp. 3047-3057
Author(s):  
Ravid Straussman ◽  
Liron Even ◽  
Shoshana Ravid
Keyword(s):  
Subcellular Localization ◽  
Tumor Cells ◽  
Cellular Localization ◽  
Myosin Ii ◽  
Prostate Tumor ◽  
Dependent Manner ◽  
Prostate Tumor Cells ◽  
Kinetics Of ◽  
Stimulation Of

To explore the involvement and regulation of the nonmuscle myosin II heavy chains isoforms, MHC-A and MHC-B in the chemotaxis of metastatic tumor cells,we analyzed the changes in phosphorylation and cellular localization of these isoforms upon stimulation of prostate tumor cells with epidermal growth factor(EGF). EGF stimulation of prostate tumor cells resulted in transient increases in MHC-A and MHC-B phosphorylation and subcellular localization with quite different kinetics. Furthermore, the kinetics of subcellular localization correlated with the in vivo kinetics of MHC-B phosphorylation but not of MHC-A phosphorylation, suggesting different modes of regulation for these myosin II isoforms. We further showed that protein kinase C (PKC) is involved in the EGF-dependent phosphorylation of MHC-A and MHC-B. To our knowledge, this is the first report demonstrating that MHC phosphorylation might regulate its subcellular localization and that the EGF signal is transmitted to MHC-A and MHC-B via PKC. The correlation between MHC-B phosphorylation and localization in response to EGF stimulation might suggest that MHC-B is the myosin II isoform that is involved in chemotaxis.

scholarly journals Relationships between proto-oncogene expression and apoptosis induced by anticancer drugs in human prostate tumor cells

1995 ◽  
Vol 1270 (1) ◽  
pp. 12-18 ◽  
Author(s):  
Birandra K. Sinha ◽  
Hiroyuki Yamazaki ◽  
Helen M. Eliot ◽  
Erasmus Schneider ◽  
Markus M. Borner ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Anticancer Drugs ◽  
Prostate Tumor ◽  
Human Prostate ◽  
Oncogene Expression ◽  
Prostate Tumor Cells ◽  
Human Prostate Tumor

scholarly journals Cytoplasmic retention of protein tyrosine kinase 6 promotes growth of prostate tumor cells

Cell Cycle ◽  
2010 ◽  
Vol 9 (20) ◽  
pp. 4190-4199 ◽  
Author(s):  
Patrick M. Brauer ◽  
Yu Zheng ◽  
Lin Wang ◽  
Angela Tyner
Keyword(s):  
Tyrosine Kinase ◽  
Tumor Cells ◽  
Protein Tyrosine Kinase ◽  
Prostate Tumor ◽  
Protein Tyrosine ◽  
Prostate Tumor Cells
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