Dataset Information

Pentostatin plus cyclophosphamide safely and effectively prevents immunotoxin immunogenicity in murine hosts.

ABSTRACT:

Purpose

The success of immunotoxin therapy of cancer is limited by host production of neutralizing antibodies, which are directed toward the Pseudomonas exotoxin A (PE) component. In this proof-of-principle study using a well-established murine model, we hypothesized that a newly developed immune depletion regimen consisting of pentostatin plus cyclophosphamide would abrogate anti-immunotoxin reactivity.

Experimental design

BALB/c hosts were injected weekly with recombinant immunotoxin (RIT) SS1P, which is an antimesothelin Fv antibody fragment genetically fused to a 38 kDa portion of PE, and has been evaluated in clinical trials. Experimental cohorts received induction chemotherapy consisting of pentostatin (P) plus cyclophosphamide (C) prior to initial RIT exposure; some cohorts received further maintenance PC therapy of varying intensity just prior to each weekly RIT challenge. Cohorts were monitored for T, B, myeloid cell depletion, and for total anti-SS1P antibody (Ab) formation.

Results

Controls uniformly developed anti-SS1P Ab after the third RIT exposure. Induction PC therapy reduced the frequency of hosts with anti-SS1P Ab. Abrogation of antibody generation was improved by maintenance PC therapy: nearly 100% of recipients of intensive PC maintenance were free of anti-SS1P Ab after 9 weekly RIT doses. The most effective PC regimen yielded the greatest degree of host B-cell depletion, moderate T-cell depletion, and minimal myeloid cell depletion.

Conclusions

Induction and maintenance PC chemotherapy safely prevented anti-immunotoxin antibody formation with uniform efficacy. These data suggest that immunotoxin therapy might be used in combination with pentostatin plus cyclophosphamide chemotherapy to improve the targeted therapy of cancer.

SUBMITTER: Mossoba ME

PROVIDER: S-EPMC3107891 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pentostatin plus cyclophosphamide safely and effectively prevents immunotoxin immunogenicity in murine hosts.

Mossoba Miriam E ME Onda Masanori M Taylor Justin J Massey Paul R PR Treadwell Shirin S Sharon Elad E Hassan Raffit R Pastan Ira I Fowler Daniel H DH

Clinical cancer research : an official journal of the American Association for Cancer Research 20110426 11

<h4>Purpose</h4>The success of immunotoxin therapy of cancer is limited by host production of neutralizing antibodies, which are directed toward the Pseudomonas exotoxin A (PE) component. In this proof-of-principle study using a well-established murine model, we hypothesized that a newly developed immune depletion regimen consisting of pentostatin plus cyclophosphamide would abrogate anti-immunotoxin reactivity.<h4>Experimental design</h4>BALB/c hosts were injected weekly with recombinant immuno ...[more]

PMID: 21521777

Similar Datasets

Project description:Background/Objectives: The rising prevalence of musculoskeletal (MSK) conditions has not been balanced by a sufficient increase in healthcare providers. Scalability challenges are being addressed through the use of artificial intelligence (AI) in some healthcare sectors, with this showing potential to also improve MSK care. Digital care programs (DCP) generate automatically collected data, thus making them ideal candidates for AI implementation into workflows, with the potential to unlock care scalability. In this study, we aimed to assess the impact of scaling care through AI in patient outcomes, engagement, satisfaction, and adverse events. Methods: Post hoc analysis of a prospective, pre-post cohort study assessing the impact on outcomes after a 2.3-fold increase in PT-to-patient ratio, supported by the implementation of a machine learning-based tool to assist physical therapists (PTs) in patient care management. The intervention group (IG) consisted of a DCP supported by an AI tool, while the comparison group (CG) consisted of the DCP alone. The primary outcome concerned the pain response rate (reaching a minimal clinically important change of 30%). Other outcomes included mental health, program engagement, satisfaction, and the adverse event rate. Results: Similar improvements in pain response were observed, regardless of the group (response rate: 64% vs. 63%; p = 0.399). Equivalent recoveries were also reported in mental health outcomes, specifically in anxiety (p = 0.928) and depression (p = 0.187). Higher completion rates were observed in the IG (79.9% (N = 19,252) vs. CG 70.1% (N = 8489); p < 0.001). Patient engagement remained consistent in both groups, as well as high satisfaction (IG: 8.76/10, SD 1.75 vs. CG: 8.60/10, SD 1.76; p = 0.021). Intervention-related adverse events were rare and even across groups (IG: 0.58% and CG 0.69%; p = 0.231). Conclusions: The study underscores the potential of scaling MSK care that is supported by AI without compromising patient outcomes, despite the increase in PT-to-patient ratios.

Project description:PurposeThis paper reports the results of a clinical study that tested the effect of systemic treatment with the botanical product Gene-Eden-VIR/Novirin on the clearance rate (also called time to clearance) of the human papillomavirus (HPV). The study compared the clearance rate in treated and untreated individuals suffering from a symptomatic HPV infection. The data on the untreated individuals were obtained by reverse engineering of the Kaplan-Meier figures in five published papers.Materials and methodsThe study included 59 treated participants. All participants were suffering from a symptomatic HPV infection prior to the commencement of treatment. The treatment was one to four capsules of Gene-Eden-VIR/Novirin per day. The duration of treatment was 2-12 months. The study included five groups of external controls with diverse characteristics.ResultsThe mean time to clearance in Gene-Eden-VIR/Novirin-treated individuals was 5.1 months or 151.5 days (95% CI: 4.2-5.9 months or 95% CI: 125.7-177.3 days, respectively). The median time to clearance was 3.5 months. The mean time to clearance in the five untreated groups ranged from 6.9 to 20.0 months (P<0.0001 for the difference between treatment group and each untreated group). Also, 100% of the participants in the treatment group were HPV free at the end of 12 months vs 53%, 52%, 65%, 20%, and 77% in the untreated control groups. The treated participants reported no adverse experiences.ConclusionThis clinical study has two major contributions. First, it showed that systemic treatment with the natural Gene-Eden-VIR/Novirin decreased the time to HPV clearance, increased the percentage of HPV-free individuals, and caused no adverse experiences in individuals suffering from a symptomatic HPV infection. Since there are no other systemic treatments for symptomatic HPV infections, this study presents highly valuable information on the clinical effects of the first treatment in this category. Second, the study presents a new method for conducting clinical studies that addresses one of the major deficiencies associated with the practice of the randomized controlled trial method.

Dataset Information

Pentostatin plus cyclophosphamide safely and effectively prevents immunotoxin immunogenicity in murine hosts.

Purpose

Experimental design

Results

Conclusions

Publications

Pentostatin plus cyclophosphamide safely and effectively prevents immunotoxin immunogenicity in murine hosts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets