scholarly journals A Conjugation Strategy to Modulate Antigen Binding and FcRn Interaction Leads to Improved Tumor Targeting and Radioimmunotherapy Efficacy with an Antibody Targeting Prostate-Specific Antigen

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3469
Author(s):  
Oskar Vilhelmsson Timmermand ◽  
Anders Örbom ◽  
Mohamed Altai ◽  
Wahed Zedan ◽  
Bo Holmqvist ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Fc Receptor ◽  
Receptor Interaction ◽  
Emission Computed Tomography ◽  
Neonatal Fc Receptor ◽  
Radionuclide Distribution ◽  
Significant Difference ◽  
The Impact

Background: The humanized monoclonal antibody (mAb) hu5A10 specifically targets and internalizes prostate cancer cells by binding to prostate specific antigen (PSA). Preclinical evaluations have shown that hu5A10 is an excellent vehicle for prostate cancer (PCa) radiotheranostics. We studied the impact of different chelates and conjugation ratios on hu5A10′s target affinity, neonatal fc-receptor interaction on in vivo targeting efficacy, and possible enhanced therapeutic efficacy. Methods: In our experiment, humanized 5A10 (hu5A10) was conjugated with DOTA or DTPA at a molar ratio of 3:1, 6:1, and 12:1. Surface plasmon resonance (SPR) was used to study antigen and FcRn binding to the antibody conjugates. [111In]hu5A10 radio-immunoconjugates were administered intravenously into BALB/c mice carrying subcutaneous LNCaP xenografts. Serial Single-photon emission computed tomography (SPECT) images were obtained during the first week. Tumors were harvested and radionuclide distribution was analyzed by autoradiography along with microanatomy and immunohistochemistry. Results: As seen by SPR, the binding to PSA was clearly affected by the chelate-to-antibody ratio. Similarly, FcRn (neonatal fc-receptor) interacted less with antibodies conjugated at high ratios of chelator, which was more pronounced for DOTA conjugates. The autoradiography data indicated a higher distribution of radioactivity to the rim of the tumor for lower ratios and a more homogenous distribution at higher ratios. Mice injected with ratio 3:1 111In-DOTA-hu5A10 showed no significant difference in tumor volume when compared to mice given vehicle over a time period of 3 weeks. Mice given a similar injection of ratio 6:1 111In-DOTA-hu5A10 or 6:1 111In-DTPA-hu5A10 or 12:1 111In-DTPA-hu5A10 showed significant tumor growth retardation. Conclusions: The present study demonstrated that the radiolabeling strategy could positively modify the hu5A10′s capacity to bind PSA and complex with the FcRn-receptor, which resulted in more homogenous activity distribution in tumors and enhanced therapy efficacy.

scholarly journals Prostate-Specific Antigen Density: A Measurement to Differentiate Benign Hypertrophy of Prostate from Prostate Carcinoma

2020 ◽  
Vol 12 (01) ◽  
pp. 44-48
Author(s):  
Chandan Kumar Nath ◽  
Bhupen Barman ◽  
Pranjal Phukan ◽  
Stephen L. Sailo ◽  
Biswajit Dey ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Sensitivity And Specificity ◽  
Prostate Volume ◽  
Specific Antigen ◽  
Prostate Specific Antigen Density ◽  
Significant Difference ◽  
The Mean ◽  
Set Up ◽  
The Individual

Abstract Background Determination of isolated prostate-specific antigen (PSA) in asymptomatic individuals has not demonstrated sufficient sensitivity and specificity to be useful in the routine evaluation of prostate disease. To enhance the accuracy of serum PSA we have used a proportion of serum PSA and prostate volume, which we refer to as prostate-specific antigen density (PSAD). Prostate volume in this study was calculated using transrectal ultrasonography (TRUS). Materials and Methods A total of 106 patients with prostatic disease clinically confined to the prostate glands were evaluated. Results and Observation The mean PSAD for prostate cancer was 0.15 ± 0.01 while that for benign hypertrophy of the prostate (BPH) was 0.11 ± 0.02 (p < 0.05). Significant difference (p < 0.05) was noted in the prostate volume in these two groups with the mean prostate volume measured by TRUS in the BPH to be 53.85 ± 9.71 mL compared with 58.14 ± 7.48 mL in the carcinoma. PSA density of 0.13 ng/mL can be used as a cutoff for the individual in our set-up who should go for prostate biopsy with sensitivity and specificity of over 90%. Conclusion These results suggest that PSAD may be useful in distinguishing BPH and prostate cancer.

A decision analytic model of prostate cancer screening using prostate-specific antigen and digital rectal exam

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5155-5155
Author(s):  
J. H. Hayes ◽  
M. J. Barry ◽  
P. W. Kantoff ◽  
J. E. Stahl
Keyword(s):  
Prostate Cancer ◽  
Life Expectancy ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Sensitivity Analyses ◽  
Base Case ◽  
Decision Analytic Model ◽  
Digital Rectal Exam ◽  
Psa Screening ◽  
The Impact

5155 Background: PSA-based screening has been widely adopted in the US although a mortality benefit has yet to be demonstrated. The disutility of screening and quality of life of men diagnosed and treated after screening are critical issues in assessing its benefit and harm. The purpose of this model is to estimate the effect of one-time screening for prostate cancer using Prostate Specific Antigen (PSA) and DRE (digital rectal exam) on life expectancy (LE) and Quality Adjusted Life Expectancy (QALE) in the context of current diagnostic and treatment practice. Methods: A semi-Markov state transition simulation describes the relevant health states. Two strategies were compared: 1) Screening - single screening PSA and DRE; 2) No Screening - patients diagnosed after developing symptoms. Markov cycle length was 1 year. Transition probabilities and utility weights were developed from review of the literature and expert opinion. Sensitivity analyses were performed on all parameters. A PSA threshold of 4 ng/mL and age 65 were used for the base case. The model was created using TreeAge software. Results: For our base case, a single screening conferred a LE benefit of 0.37 y (15.86 vs 15.49 y) and a QALE benefit of 0.20 QALYs (15.62 vs 15.42 QALYs). Predicted 10 y cancer specific survival for screen-diagnosed men was 95.7% vs SEER 97.7%. The model predicted 9.5% of screened patients would have metastatic disease at diagnosis vs 5% in SEER (4% unknown stage); in unscreened men, this rate was 18/100,000 vs 15/100,000 in SEER. Sensitivity Analyses of Utilities (SA): The single screen model was relatively insensitive to SA of utilities: a 20% single cycle toll on one-time PSA screening disutility was required to eliminate the benefit of screening. The disutility of positive PSA with negative biopsy slightly affected QALE: a toll of 0.25 QALYs decreased QALE from 15.62 to 15.61 QALYs. Conclusions: Our model reveals a modest benefit to one-time screening for prostate cancer. This one-time screening model is relatively insensitive to utility SA; however, the importance of incorporating psychological effects of PSA screening in recurrent screening is to be determined. The impact of serial screening, lead time, PSA threshold, and cost effectiveness on LE and QALE is being analyzed. No significant financial relationships to disclose.

The prognostic value of mid-treatment prostate-specific antigen level in patients receiving salvage radiotherapy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 289-289
Author(s):  
Jason Homza ◽  
John T. Nawrocki ◽  
Harmar D. Brereton ◽  
Christopher A. Peters
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Salvage Radiotherapy ◽  
Clinical Failure ◽  
Treatment Intensification ◽  
Significant Difference ◽  
Group 2 ◽  
Group 1

289 Background: Salvage radiotherapy (SRT) may be employed as a potentially curative intervention for patients experiencing biochemical failure (serum prostate-specific antigen [PSA] ≥ 0.2 ng/mL) after prostatectomy for localized prostate cancer. Patients not showing a favorable response to SRT alone may require additional therapies and may benefit from earlier identification of this need. Methods: 131 consecutive patients received SRT during the timeframe of this study. 76 were deemed eligible based on the following criteria: prostatic adenocarcinoma diagnosis receiving SRT, no clinical evidence of metastasis, no hormone use prior to/during SRT, serum PSA measurement halfway through SRT, and minimum follow-up time of 3 months. Median follow-up time was 51.6 months. Eligible patients were divided into three groups based on PSA response by the midpoint of treatment: no change, decrease, or increase in PSA. The primary endpoint of the study was clinical failure (measured from SRT completion), defined as serum PSA value ≥0.2ng/mL above the post-radiotherapy nadir, initiation of androgen deprivation therapy, development of bone metastasis, or death from prostate cancer. Results: 13.1% experienced no change in PSA halfway through SRT (group 0), 68.4% of patients experienced a decrease (group 1), 18.4% experienced an increase (group 2). Four-year freedom from clinical failure was 60.0% for group 0, 58.3% for group 1, and 41.7% for group 2. Median time to clinical failure was 71.7 months for group 1, 26.8 months for group 2, and was not reached for group 0. Pairwise multiple comparison demonstrated a significant difference in four-year freedom from clinical failure between groups 1 and 2 (p = 0.036). Conclusions: These data strongly suggest that changes in PSA are apparent midway through SRT and are associated with 4-year freedom from clinical failure. Further study is warranted to determine whether mid-treatment PSA during SRT may be used to identify a subset of patients that may benefit from treatment intensification.

scholarly journals Role of Androgen Deprivation Therapy for Node-Positive Prostate Cancer

2009 ◽  
Vol 27 (1) ◽  
pp. 100-105 ◽  
Author(s):  
Yu-Ning Wong ◽  
Stephen Freedland ◽  
Brian Egleston ◽  
Gary Hudes ◽  
J. Sanford Schwartz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Nodes ◽  
Androgen Deprivation Therapy ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Regional Lymph Nodes ◽  
Node Positive ◽  
Survival Difference ◽  
Significant Difference ◽  
The Impact

Purpose To determine the impact of adjuvant androgen deprivation therapy (ADT) for patients who have node-positive prostate cancer in the prostate-specific antigen (PSA) era. Patients and Methods We used linked Surveillance, Epidemiology and End Results-Medicare data to construct a cohort of men who underwent radical prostatectomy (RP) between 1991 and 1999 and who had positive regional lymph nodes. We classified men as receiving adjuvant ADT if they received ADT within 120 days of RP, and we compared them to the men who had not received adjuvant ADT. We used propensity scores to balance potential confounders of receiving adjuvant ADT (ie, tumor characteristics, extent of nodal disease, demographics, receipt of radiation therapy) and Cox proportional hazard methods to measure the impact of adjuvant ADT on overall survival (OS), stratified by propensity score quintile. We conducted a sensitivity analysis that used 90, 150, 180, and 365 days as the definition for adjuvant ADT. Results A total of 731 men were identified, 209 of whom received ADT within 120 days of RP. There was no statistically significant difference in OS between the adjuvant ADT and non-ADT group (HR, 0.97; 95% CI, 0.71 to 1.27). There was no statistically significant survival difference with 90, 150, 180, and 365 days as the adjuvant ADT definition. Conclusion Deferring immediate ADT in men with positive lymph nodes after RP may not significantly compromise survival. Because observational studies should be considered hypothesis-generating studies, these results should be validated in a prospective fashion in a similar patient population.

scholarly journals Prostate-specific antigen and (free prostate-specific antigen/ prostate-specific antigen) ratio in patients with Benign Prostatic Hyperplasia and Prostate Cancer

2020 ◽  
Vol 1 (01) ◽  
pp. 17-25
Author(s):  
Amal A. Hussein ◽  
Rayah S. Baban ◽  
Alaa G. Hussein
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Case Control Study ◽  
Specific Antigen ◽  
Control Group ◽  
Inverse Association ◽  
Control Groups ◽  
Significant Difference ◽  
And Control ◽  
Control Study

Background: Prostate cancer is one of the most common cancers in menworldwide. Many markers are suggested as markers of prostate cancer with differentspecificity and sensitivity.Objective : The present study’s main aim is to examine the possible utility ofprostate-specific antigen indices as markers of prostate cancer.Methods: A case-control study was conducted in the Department of Chemistry andBiochemistry, College of Medicine, Al- Nahrain University, Baghdad, Iraq from July2018 till March 2019, includes 84 subjects divided into three groups:Twenty Four patients with prostate cancer (PCA), thirty patients with benignprostatic hyperplasia (BPH) and thirty healthy subjects as a control group wereexamined in this study.Thirty healthy volunteer subjects were asked to be involved in this study as a controlgroup. Blood samples from these patients were collected before obtaining a prostaticbiopsy. Serum PSA, fPSA levels were quantified by the ELISA technique.Results: PSA cut-off value was found to be more than 9.57 ng/ml for Prostate Cancerpatients, values range between 3.17 - 9.57 ng/ml for BPH patients and cut-off valuefor control was found to be less than 3.17 ng/ml, while serum (fPSA/PSA) % cut-offvalue was less than 11.1% for Prostate Cancer patients, values range between 11.1% -31 % for BPH patients, and cut-off value was greater than 31% for the control group.Conclusion: There is a highly significant difference in serum PSA levels and(fPSA/PSA)% between the prostate cancer and control groups. Body mass indexshowed an inverse association with the risk of prostate cancer.

scholarly journals Functional and oncological outcomes of salvage external beam radiotherapy following robot-assisted radical prostatectomy in a Canadian cohort

2017 ◽  
Vol 12 (2) ◽  
pp. 45-9
Author(s):  
Khaled Ajib ◽  
Marc Zanaty ◽  
Mansour Alnazari ◽  
Emad Rajih ◽  
Pierre-Alain Hueber ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
External Beam Radiotherapy ◽  
Specific Antigen ◽  
Urinary Continence ◽  
Robot Assisted ◽  
Time Points ◽  
Canadian Experience ◽  
Significant Difference ◽  
The Impact

Introduction: We sought to determine the impact of salvage radiotherapy (SRT) on oncological and functional outcomes of patients with prostate cancer after biochemical recurrence (BCR) following robot-assisted radical prostatectomy (RARP).Methods: Data of 70 patients with prostate cancer treated with SRT after developing BCR were retrospectively analyzed from a prospectively collected RARP database of 740 men. Oncological (prostate- specific antigen [PSA]) and functional (pads/day, International Prostate Symptom Score [IPSS], and Sexual Health Inventory for Men [SHIM]) outcomes were reported at six, 12, and 24 months after RT and adjusted for pre-SRT status.Results: Men who underwent SRT had a mean age, PSA, and time from radical prostatectomy (RP) to RT of 61.8 years (60.1‒63.6), 0.5 ng/ml (0.2‒0.8), and 458 days (307‒747), respectively. Freedom from biochemical failure (FFBF) post-SRT, defined as a PSA nadir <0.2 ng/mL, was observed in 89%, 93%, and 81%, at six, 12, and 24 months, respectively. Undetectable PSA was observed in 14%, 35%, and 40% at the same time points, respectively. There was no significant difference in urinary continence post-SRT (p=0.56). Rate of strict continence (0 pads/day) was 71% at 24 months compared to 78% pre-SRT. Mean IPSS at six, 12, and 24 months was 3.4, 3.6, and 3.6, respectively compared to pre-RT score of 3.3 (p=0.61). The mean SHIM score pre-SRT was comparable at all time points following treatment (p=0.86).Conclusions: In this unique Canadian experience, it appears that early SRT is highly effective for the treatment of BCR following RARP with little impact on urinary continence and potency outcomes.

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