Immunotherapy of equine sarcoid: dose-escalation trial for the use of chimeric papillomavirus-like particles.
Equine sarcoids are fibrosarcoma-like skin tumours with a prevalence of approximately 1-2 %. Strong evidence exists for a causative role of bovine papillomavirus (BPV) type 1 or type 2 in the development of sarcoids. No effective treatment of equine sarcoid is available and after surgical excision relapse of the tumours is very frequent. We developed chimeric virus-like particles (CVLPs) of BPV 1 L1-E7 for the immunotherapy of equine sarcoid. In a phase I clinical trial 12 horses suffering from equine sarcoid with an average number of more than 22 tumours per animal were vaccinated in a dose-escalation setting. The animals were followed-up for 63 days, eight of the twelve horses were followed-up for more than a year and side-effects, humoral immune responses and tumour appearance were recorded. BPV DNA was detected in tumours of 11 cases. CVLPs were well tolerated in all dose groups, a robust anti-L1 antibody response was induced in all but one of the horses. Anti-E7 antibodies were detected in five of the 12 animals at low titres. Two animals showed a clear improvement of the clinical status after treatment, i.e. the number of the tumours per horse was reduced. In another horse regression of five sarcoids was observed; three of them relapsed during the study. Two animals showed tumour regression as well as growth of new sarcoids. In two horses the clinical status remained unchanged, in another two horses growth of existing tumours or growth of additional tumours was observed. The remaining three animals showed simultaneously regression and growth of existing tumours. Neither the humoral immune responses nor the observed effects on the tumours was correlated with the dose group.
Mattil-Fritz
Stephanie
S
Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
Scharner
Doreen
D
Universität Leipzig, Veterinärmedizinische Fakultät, Chirurgische Tierklinik, Leipzig, Germany.
Piuko
Konrad
K
Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
Thönes
Nadja
N
Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
Gissmann
Lutz
L
Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
Müller
Hermann
H
Universität Leipzig, Veterinärmedizinische Fakultät, Institut für Virologie Leipzig, Germany.
Müller
Martin
M
Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D000917:Antibody Formation; D001706:Biopsy; D052688:Bovine papillomavirus 1 / Q000235:genetics* / Q000302:isolation & purification*; D002678:Chimera; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology / Q000601:surgery / Q000662:veterinary / Q000821:virology*; D006734:Horse Diseases / Q000276:immunology / Q000601:surgery / Q000821:virology*; D006736:Horses; D007167:Immunotherapy; D008297:Male; D030361:Papillomavirus Infections / Q000276:immunology / Q000601:surgery / Q000662:veterinary*; D012008:Recurrence; D012507:Sarcoidosis / Q000276:immunology / Q000601:surgery / Q000662:veterinary* / Q000821:virology*
D000914:Antibodies, Viral; D004279:DNA, Viral