Fred Hutchinson Cancer Research Center

About: Fred Hutchinson Cancer Research Center is a nonprofit organization based out in Cape Town, South Africa. It is known for research contribution in the topics: Population & Transplantation. The organization has 12322 authors who have published 30954 publications receiving 2288772 citations. The organization is also known as: Fred Hutch & The Hutch.

Efficacy Trial of a DNA/rAd5 HIV-1 Preventive Vaccine

Abstract: Background A safe and effective vaccine for the prevention of human immunodeficiency virus type 1 (HIV-1) infection is a global priority. We tested the efficacy of a DNA prime–recombinant adenovirus type 5 boost (DNA/rAd5) vaccine regimen in persons at increased risk for HIV-1 infection in the United States. Methods At 21 sites, we randomly assigned 2504 men or transgender women who have sex with men to receive the DNA/rAd5 vaccine (1253 participants) or placebo (1251 participants). We assessed HIV-1 acquisition from week 28 through month 24 (termed week 28+ infection), viral-load set point (mean plasma HIV-1 RNA level 10 to 20 weeks after diagnosis), and safety. The 6-plasmid DNA vaccine (expressing clade B Gag, Pol, and Nef and Env proteins from clades A, B, and C) was administered at weeks 0, 4, and 8. The rAd5 vector boost (expressing clade B Gag-Pol fusion protein and Env glycoproteins from clades A, B, and C) was administered at week 24. Results In April 2013, the data and safety monitoring board re...

Early Adiposity Rebound and the Risk of Adult Obesity

Abstract: Objective. At 5 to 6 years of age, body fatness normally declines to a minimum, a point called adiposity rebound (AR), before increasing again into adulthood. We determined whether a younger age at AR was associated with an increased risk of adult obesity and whether this risk was independent of fatness at AR and parent obesity. Design. A retrospective cohort study using lifelong height and weight measurements recorded in outpatient medical records. Setting. Group Health Cooperative of Puget Sound (GHC), a health maintenance organization based in Seattle, Washington. Participants. All 390 GHC members (and their parents) born at GHC between January 1, 1965, and January 1, 1971, who had at least one recorded adult height and weight measurement plus two visits with recorded height and weight measurements in each of three age intervals: 1.5 to 4, 4 to 8, and 8 to 16 years. Main Outcome Measures. We calculated the mean body mass index (BMI) of each subject during young adulthood (age 21 to 29 years) and the BMI of the parents when each subject was 1.5 years of age. Adult obesity was defined as a BMI ≥27.8 for males and ≥27.3 for females. Curves were fit to each subject9s BMI values between ages 1.5 and 16 years, and the age and BMI at AR were calculated from these curves. Subjects were divided into tertiles of age at AR (early, middle, and late), BMI at AR, and parent BMI (heavy, medium, and lean). Results. The mean age at AR was 5.5 years, and 15% of the cohort was obese in young adulthood. Adult obesity rates were higher in those with early versus late AR (25% vs 5%), those who were heavy versus lean at AR (24% vs 4%), those with heavy versus lean mothers (25% vs 5%), and those with heavy versus lean fathers (21% vs 5%). After adjusting for parent BMI and BMI at AR, the odds ratio for adult obesity associated with early versus late AR was 6.0 (95% CI, 1.3–26.6). Conclusion. An early AR is associated with an increased risk of adult obesity independent of parent obesity and the BMI at AR. Future research should examine the biological and behavioral determinants of AR.

Factors Associated with the Development of Cross-Reactive Neutralizing Antibodies during Human Immunodeficiency Virus Type 1 Infection

Abstract: The characterization of the cross-reactive, or heterologous, neutralizing antibody responses developed during human immunodeficiency virus type 1 (HIV-1) infection and the identification of factors associated with their generation are relevant to the development of an HIV vaccine. We report that in healthy HIV-positive, antiretroviral-naive subjects, the breadth of plasma heterologous neutralizing antibody responses correlates with the time since infection, plasma viremia levels, and the binding avidity of anti-Env antibodies. Anti-CD4-binding site antibodies are responsible for the exceptionally broad cross-neutralizing antibody responses recorded only in rare plasma samples. However, in most cases examined, antibodies to the variable regions and to the CD4-binding site of Env modestly contributed in defining the overall breadth of these responses. Plasmas with broad cross-neutralizing antibody responses were identified that targeted the gp120 subunit, but their precise epitopes mapped outside the variable regions and the CD4-binding site. Finally, although several plasmas were identified with cross-neutralizing antibody responses that were not directed against gp120, only one plasma with a moderate breadth of heterologous neutralizing antibody responses contained cross-reactive neutralizing antibodies against the 4E10 epitope, which is within the gp41 transmembrane subunit. Overall, our study indicates that more than one pathway leads to the development of broad cross-reactive neutralizing antibodies during HIV infection and that the virus continuously escapes their action.

PROVENGE (Sipuleucel-T) in Prostate Cancer: The First FDA-Approved Therapeutic Cancer Vaccine

Abstract: Sipuleucel-T (PROVENGE; Dendreon) is the first therapeutic cancer vaccine to be approved by the U.S. Food and Drug Administration. In men who have metastatic castration-resistant prostate cancer with no or minimal symptoms, sipuleucel-T prolongs median survival by 4.1 months compared with results in those treated with placebo. At 3 years, the proportion of patients in the vaccine group who were alive was 50% higher than that in the control group (31.7% versus 21.7%, respectively). Sipuleucel-T, which is designed to elicit an immune response to prostatic acid phosphatase, uses the patient's own immune system to recognize and combat his cancer. Currently, no other agents are available that offer a survival benefit for this population of asymptomatic patients who have not been treated with chemotherapy, except for docetaxel (whose inherent toxicities often lead patients and physicians to delay administration until symptoms develop). Straightforward strategies to increase the efficacy of sipuleucel-T are likely to provide even greater benefit. The preclinical and clinical development of sipuleucel-T is reviewed, and approaches to enhance efficacy are considered herein.