Recombinant and Natural Human Interferons: Analysis of the Incidence and Clinical Impact of Neutralizing Antibodies

被引:8
|
作者
Strayer, David R. [1 ]
Carter, William A. [1 ]
机构
[1] Hemispherx Biopharma Inc, Dept Clin Res, Philadelphia, PA 19103 USA
来源
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH | 2012年 / 32卷 / 03期
关键词
C VIRUS-INFECTION; ALPHA ANTIBODIES; THERAPY; IFN; LEUKEMIA; BETA-1A;
D O I
10.1089/jir.2011.0069
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This review summarizes and analyzes the clinical outcomes following treatment of a wide range of diseases with recombinant interferons (r-IFNs) and/or natural interferons (n-IFNs). The investigation focuses on the frequency of neutralizing antibodies (NABs) directed against IFN, which are formed during treatment and their clinical impact. r-IFNs (alpha-2 alpha, alpha-2b, beta-1 alpha, and beta-1b) induced seroconversion with generation of NABs in 17.2% of patients studied. The highest incidence of NABs occurred in macular degeneration (61.4%) with the lowest in multiple sclerosis (14.7%). The incidence of antibodies induced against n-IFNs was very low (< 0.2%) and was significantly less than that seen for r-IFNs (P < 0.0001). Overall, the fraction of relapsed and refractory patients is statistically greater in NAB positive patients compared to NAB negative patients (< 0.0001), whereas the percentage of responding patients is higher in the NAB negative cohort (P < 0.001). Finally, we also analyzed relapsed and refractory NAB positive patients who switched treatment to n-IFN, such as leukocyte derived Alferon N Injection (R) (alpha-n3) or Wellferon (R) (alpha-n1). Overall, in 33/40 (82%) of these relapsed or refractory patients, switching to n-IFNs restored the clinical response. This result is consistent with serology studies showing that the NABs directed against r-IFNs do not effectively cross-react with n-IFNs.
引用
收藏
页码:95 / 102
页数:8
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