Monitoring circulating prostate tumor cells after tumor resection by in vivo flow cytometry

2018 ◽  
Author(s):  
Xunbin Wei ◽  
Nan Ding ◽  
Chengying Xie ◽  
Zhangru Yang ◽  
Yuanzhen Suo ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Tumor Cells ◽  
Tumor Resection ◽  
Prostate Tumor ◽  
In Vivo Flow Cytometry ◽  
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

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 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.

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