title: Active specific immunotherapy with Newcastle-disease-virus-modified autologous tumor cells following resection of liver metastases in colorectal cancer. First evaluation of clinical response of a phase II-trial.
abstract: A group of 23 colorectal cancer patients were treated by a new type of active specific immunotherapy (ASI) following complete surgical resection of liver metastases (RO resection). For ASI treatment we used a vaccine consisting of 1 x 10(7) autologous, irradiated (200 Gy) metastases-derived tumor cells incubated with 32 hemagglutination units (HU) of Newcastle disease virus (NDV). The adjuvant vaccine therapy was started 2 weeks after surgery and was repeated five times at 14-days intervals followed by one boost 3 months later. The delayed-type hypersensitivity (DTH) skin reactions to the vaccine were measured as well as the DTH reactions to a challenge test of 1 x 10(7) non-virus-modified autologous tumor cells from liver metastases or 1 x 10(7) autologous normal liver cells. In addition 32 HU NDV alone and a standard antigen test (Merieux test) were applied pre- and post-vaccination. The vaccination was well tolerated. In 13 of 23 patients an increasing reactivity against the vaccine was observed during the vaccination procedure. Nine patients (40%) experienced an increased DTH reactivity against autologous tumor cells following vaccination, while 17% or fewer showed an increased reactivity to Merieux test antigens, NDV, or normal liver cells. The increased antitumor response was not correlated to responsiveness to NDV alone, autologous liver cells, enzymes and culture medium used for vaccine preparation or standard antigens (Merieux test). After a follow-up of at least 18 months 61% of the vaccinated patients developed tumor recurrence in comparison to 87% of a matched control groups from the same institution that had been only surgically treated. The results of this phase II trial are encouraging and should stimulate further prospective randomized studies.
authors.affiliation: Section of Surgical Oncology, University of Heidelberg, Federal Republic of Germany.
authors.forename: P
authors.initials: P
authors.lastname: Schlag
authors.forename: M
authors.initials: M
authors.lastname: Manasterski
authors.forename: T
authors.initials: T
authors.lastname: Gerneth
authors.forename: P
authors.initials: P
authors.lastname: Hohenberger
authors.forename: M
authors.initials: M
authors.lastname: Dueck
authors.forename: C
authors.initials: C
authors.lastname: Herfarth
authors.forename: W
authors.initials: W
authors.lastname: Liebrich
authors.forename: V
authors.initials: V
authors.lastname: Schirrmacher
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology; D016233:Immunotherapy, Active / Q000009:adverse effects; D008113:Liver Neoplasms / Q000556:secondary* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009522:Newcastle disease virus / Q000276:immunology*