A trial of SGN-00101 (HspE7) to treat high-grade anal intraepithelial neoplasia in HIV-positive individuals.
OBJECTIVE
To test a therapeutic vaccine consisting of a fusion of the human papillomavirus (HPV) 16 E7 protein and the Mycobacterium bovis heat shock protein 65 (SGN-00101) to treat high-grade anal intraepithelial neoplasia (HG-AIN) in HIV-positive individuals.


METHODS
A phase I/II trial with three cohorts of five participants each, sequentially assigned to receive 100, 500 or 1000 microg SGN-00101, injected three times subcutaneously in alternating thighs at 4-week intervals. Anal disease was assessed at baseline, 8, 12, 24 and 48 weeks and was classified as the more severe of anal cytology and anal biopsy. Anal HPV DNA was detected using L1 consensus primer-based PCR followed by type-specific probing and dot-blot hybridization (DBH). HPV16, 18 and 31 DNA copy numbers were measured using quantitative real-time PCR.


METHODS
University-based research clinic.


METHODS
Thirteen HIV-positive men and two HIV-positive women with HG-AIN.


RESULTS
There were no drug-related serious adverse events or significant changes in HIV viral load and CD4/CD8 ratio. At 48 weeks, two of five participants in both the 100 and 500 microg cohorts regressed to AIN 1 and one of five participants in the 1000 microg cohort regressed to atypical squamous cells of undetermined significance (ASC-US). All participants had at least one oncogenic HPV type at baseline. Three of five (60%) participants who regressed to AIN 1 or ASC-US became HPV-negative using DBH and real-time PCR, compared with none of 10 participants with no clinical response (P = 0.02).


CONCLUSIONS
SGN-00101 was well tolerated in HIV-positive individuals, with preliminary evidence for clinical activity.
Palefsky
Joel M
JM
Department of Medicine, University of California-San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143, USA. joelp@medicine.ucsf.edu
Berry
J Michael
JM
Jay
Naomi
N
Krogstad
Marya
M
Da Costa
Maria
M
Darragh
Teresa M
TM
Lee
Jeannette Y
JY
D000328:Adult; D001005:Anus Neoplasms / Q000276:immunology / Q000628:therapy* / Q000821:virology; D001426:Bacterial Proteins / Q000276:immunology; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002278:Carcinoma in Situ / Q000276:immunology / Q000628:therapy* / Q000821:virology; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006679:HIV Seropositivity / Q000150:complications* / Q000276:immunology; D015497:HIV-1 / Q000302:isolation & purification; D052162:Human papillomavirus 16 / Q000276:immunology; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification; D050725:Papillomavirus E7 Proteins / Q000276:immunology; D030361:Papillomavirus Infections / Q000150:complications / Q000628:therapy; D011993:Recombinant Fusion Proteins; D014611:Vaccination / Q000379:methods; D019562:Viral Load; D014765:Viral Vaccines / Q000627:therapeutic use
D001426:Bacterial Proteins; D019496:Cancer Vaccines; D018834:Chaperonin 60; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D014765:Viral Vaccines; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins