scholarly journals The change in expression of prostate-specific membrane antigen in circulating tumor cells during treatments for castration-resistant prostate cancer

2018 ◽  
Vol 29 ◽  
pp. ix68
Author(s):  
N. Nagaya ◽  
M. Kanayama ◽  
M. Nagata ◽  
S. Horie
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Prostate Specific Membrane Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Specific Membrane

Heterogeneity of prostate-specific membrane antigen (PSMA) expression in classic and apoptotic circulating tumor cells (CTC) in metastatic castration-resistant prostate cancer (mCRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 198-198 ◽  
Author(s):  
Karen A. Autio ◽  
Aseem Anand ◽  
Rachel Krupa ◽  
Jessica Louw ◽  
Zaina Arslan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Specific Antigen ◽  
Cytotoxic Agents ◽  
Prostate Specific Membrane Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Specific Membrane ◽  
Psma Expression

198 Background: Prostate-specific membrane antigen (PSMA) is a folate hydrolase expressed on the surface of PC cells that has been used as a target to detect disease and selectively deliver cytotoxic agents and radionuclides. The ability to detect PSMA levels on circulating tumor cells (CTCs) may identify patients likely to benefit from such targeted therapy. Technology developed by Epic Sciences utilizes high definition imaging of plated nucleated cells. Methods: Blood samples were obtained from patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Cells were stained for CK, CD45, PSMA and categorized as classic CTC (CK+, CD45-, intact/morphologically distinct nuclei) or apoptotic CTC (CK+, CD45-, morphology suggesting apoptosis). Clinical data including treatment, metastatic sites, Veridex CellSearch CTC enumeration, prostate-specific antigen, and alkaline phosphatase was collected. Results: Fourteen pts with mCRPC, including eight with serial samples were analyzed (33 samples in total). At the first draw (t1), classic CTC were detected in 13 pts (93%), (median two cells/ml, range 0 to 40 cells/ml) and apoptotic CTC in 14 pts (100%) (median four cells/ml, range 1 to 18 cells/ml), including six pts (42%) with no CTC by Veridex CellSearch. PSMA expression was detected in five pts (36%) with classic CTC of which a median of 32% of cells (range 5 to 100%) expressed the antigen. Similar intra-patient heterogeneity was seen for the 10 pts (71.4%) with PSMA+ apoptotic CTCs (median 33.5%, range 11 to 75% cells). During treatment, often with more complete androgen suppression, PSMA was detected in 3 of the 8 (38%) pts with no PSMA+ classic CTCs at t1. The presence of PSMA expression in apoptotic CTCs did not appear to change while on therapy. Conclusions: A larger percentage of PSMA expression was seen in mCRPC pts in apoptotic CTC (10 out of 14) than classic CTC (5 out of 14) at t1, with intra-patient cell heterogeneity of PSMA expression in both CTC populations. Serial measures suggest dynamic changes in PSMA expression over time. The threshold of detectable cells and proportion and degree of PSMA expression that associates with drug sensitivity is unknown. Larger samples of pts at discrete time points on therapy are underway to further elucidate the potential clinical relevance.

Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in men with prostate cancer previously treated with taxane.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 107-107 ◽  
Author(s):  
Daniel Peter Petrylak ◽  
Philip W. Kantoff ◽  
Anthony E. Mega ◽  
Robert Dreicer ◽  
Richard C. Frank ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Hematological Parameters ◽  
Phase 1 ◽  
Prostate Specific Membrane Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Previously Treated ◽  
Specific Membrane

107 Background: The abundant expression of prostate specific membrane antigen (PSMA) type II transmembrane glycoprotein on prostate cancer cells provides a rationale for antibody therapy. PSMA ADC, a fully humanized antibody to PSMA linked to the potent antitubulin agent monomethyl auristatin E (MMAE), binds PSMA and is internalized within the prostate cancer cell where cleavage and release of free MMAE occur, causing cell cycle arrest and apoptosis. We report results from an ongoing phase 1 dose escalation study of PSMA ADC in patients (pts) with taxane-refractory metastatic castration-resistant prostate cancer (metCRPC). Methods: Eligibility requirements include metCRPC after taxane-containing regimen and ECOG status of 0 or 1. PSMA ADC was administered by IV infusion Q3W for up to 4 cycles. Adverse events, PK, PSA, circulating tumor cells, clinical disease progression and immunogenic response to PSMA ADC were assessed. Serum PSMA ADC and total antibody were measured by ELISA, and free MMAE was measured by LC/MS/MS. Dosing cohorts have ranged from 0.4 mg/kg to 2.2 mg/kg. Results: 26 pts have enrolled in six dosing cohorts (0.4, 0.7, 1.1, 1.6, 1.8, 2.0 mg/kg). Treatment has to date been generally well tolerated with the most commonly seen adverse event being fatigue and the most common laboratory abnormalities being reversible changes in liver and hematological parameters. Antitumor activity manifested as reductions in PSA, circulating tumor cells and/or bone pain has been observed in the higher dose cohorts and appears to be dose-related. Exposure to PSMA ADC increased with dose and was ∼1,000-fold greater than MMAE exposure. Similar PK metrics were observed after the first and third doses. Dosing at the 2.2 mg/kg cohort is continuing and an MTD has not yet been reached. Conclusions: In pts with metCRPC previously treated with taxane PSMA ADC has exhibited dose-related antitumor activity. The MTD has not yet been reached and enrollment is ongoing at higher dose levels.

scholarly journals PSMA targeting in metastatic castration-resistant prostate cancer: where are we and where are we going?

2021 ◽  
Vol 13 ◽  
pp. 175883592110538
Author(s):  
Anne-Laure Giraudet ◽  
David Kryza ◽  
Michael Hofman ◽  
Aurélie Moreau ◽  
Karim Fizazi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Membrane Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Treatment ◽  
Normal Tissues ◽  
Drug Conjugates ◽  
Castration Resistant ◽  
Current State ◽  
Important Addition ◽  
Specific Membrane

Prostate-specific membrane antigen (PSMA) is highly expressed on the membrane of most prostate cancer cells and to a lesser extent in normal tissues. Many vectors targeting this protein have been created over the past decade and numerous clinical studies have positively demonstrated the tolerance and efficacy of radiolabeled prostate-specific membrane antigen ligands for PSMA radioligand therapy (PRLT). Preliminary results are encouraging that PRLT will become an important addition to the current therapeutic options in a number of settings. Improvement in radiopharmaceutical targeting and combination with other oncological agents are under investigation to further improve its therapeutic efficacy. These encouraging results have led to the development of other therapies using PSMA as a target, such as PSMA–targeted chimeric antigen receptor T-cells, PSMA–targeted antibody drug conjugates, and PSMA–targeted bi-specific T-cell-directed therapy. This narrative review details the current state and advancements in prostate-specific membrane antigen targeting in prostate cancer treatment.

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