Dataset Information

Selective Depletion of Antigen-Specific Antibodies for the Treatment of Demyelinating Disease.

ABSTRACT: Current treatments for antibody-mediated autoimmunity are associated with lack of specificity, leading to immunosuppressive effects. To overcome this limitation, we have developed a class of antibody-based therapeutics for the treatment of autoimmunity involving antibodies that recognize the autoantigen, myelin oligodendrocyte glycoprotein (MOG). These agents ("Seldegs," for selective degradation) selectively eliminate antigen (MOG)-specific antibodies without affecting the levels of antibodies of other specificities. Seldeg treatment of mice during antibody-mediated exacerbation of experimental autoimmune encephalomyelitis by patient-derived MOG-specific antibodies results in disease amelioration. Consistent with their therapeutic effects, Seldegs deliver their targeted antibodies to Kupffer and liver sinusoidal endothelial cells that are known to have tolerogenic effects. Our results show that Seldegs can ameliorate disease mediated by MOG-specific antibodies and indicate that this approach also has the potential to treat other autoimmune diseases where the specific clearance of antibodies is required.

SUBMITTER: Sun W

PROVIDER: S-EPMC7934575 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Selective Depletion of Antigen-Specific Antibodies for the Treatment of Demyelinating Disease.

Sun Wei W Khare Priyanka P Wang Xiaoli X Challa Dilip K DK Greenberg Benjamin M BM Ober Raimund J RJ Ward E Sally ES

Molecular therapy : the journal of the American Society of Gene Therapy 20201117 3

Current treatments for antibody-mediated autoimmunity are associated with lack of specificity, leading to immunosuppressive effects. To overcome this limitation, we have developed a class of antibody-based therapeutics for the treatment of autoimmunity involving antibodies that recognize the autoantigen, myelin oligodendrocyte glycoprotein (MOG). These agents ("Seldegs," for selective degradation) selectively eliminate antigen (MOG)-specific antibodies without affecting the levels of antibodies ...[more]

PMID: 33212299

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Project description:ImportanceProstate-specific antigen (PSA) screening for prostate cancer is controversial. Experts have suggested more personalized or more conservative strategies to improve benefit-risk tradeoffs, but the value of these strategies-particularly when combined with increased conservative management for low-risk cases-is uncertain.ObjectivesTo evaluate the potential cost-effectiveness of plausible PSA screening strategies and to assess the value added by increased use of conservative management among low-risk, screen-detected cases.Design, setting, and participantsA microsimulation model of prostate cancer incidence and mortality was created. A simulated contemporary cohort of US men beginning at 40 years of age underwent 18 strategies for PSA screening. Treatment strategies included (1) contemporary treatment practices based on age and cancer stage and grade observed in the Surveillance, Epidemiology, and End Results program in 2010 or (2) selective treatment practices whereby cases with a Gleason score lower than 7 and clinical T2a stage cancer or lower are treated only after clinical progression, and all other cases undergo contemporary treatment practices. National and trial data on PSA growth, screening and biopsy patterns, incidence of prostate cancer, treatment distributions, treatment efficacy, mortality, health-related quality of life, and direct medical expenditure were analyzed. Data were collected from March 18, 2009, to August 15, 2014, and analyzed from November 20, 2012, to December 11, 2015.InterventionsEighteen screening strategies that vary by start and stop age, screening interval, and criteria for biopsy referral and contemporary or selective treatment practices.Main outcomes and measuresLife-years (LYs), quality-adjusted life-years (QALYs), direct medical expenditure, and cost per LY and QALY gained.ResultsAll 18 screening strategies were associated with increased LYs (range, 0.03-0.06) and costs ($263-$1371) compared with no screening, with the cost ranging from $7335 to $21 649 per LY. With contemporary treatment, only strategies with biopsy referral for PSA levels higher than 10.0 ng/mL or age-dependent thresholds were associated with increased QALYs (0.002-0.004), and only quadrennial screening of patients aged 55 to 69 years was potentially cost-effective in terms of cost per QALY (incremental cost-effectiveness ratio, $92 446). With selective treatment, all strategies were associated with increased QALYs (0.002-0.004), and several strategies were potentially cost-effective in terms of cost per QALY (incremental cost-effectiveness ratio, $70 831-$136 332).Conclusions and relevanceFor PSA screening to be cost-effective, it needs to be used conservatively and ideally in combination with a conservative management approach for low-risk disease.

Dataset Information

Selective Depletion of Antigen-Specific Antibodies for the Treatment of Demyelinating Disease.

Publications

Selective Depletion of Antigen-Specific Antibodies for the Treatment of Demyelinating Disease.

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