Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-5-15
pubmed:abstractText
Vaccination against tumor antigens has been shown to be a safe and efficacious prophylactic and therapeutic antitumor treatment in many animal models. Clinical studies in humans indicate that specific immunotherapy can also result in clinical benefits. The active pharmaceutical ingredient in such vaccines can be DNA, RNA, protein, or peptide and can be administered naked, encapsulated, or after delivery in vitro into cells that are then adoptively transferred. One of the easiest, most versatile and theoretically safest technologies relies on the direct injection of naked messenger RNA (mRNA) that code for tumor antigens. We and others have shown in mice that intradermal application of naked mRNA results in protein expression and the development of an immune response. We used this protocol to vaccinate 15 melanoma patients. For each patient a growing metastasis was removed, total RNA was extracted, reverse-transcribed, amplified, and cloned. Libraries of cDNA were transcribed to produce unlimited amounts of copy mRNA. Autologous preparations were applied intradermally in combination with granulocyte macrophage colony-stimulating factor as adjuvant. We demonstrate here that such treatment is feasible and safe (phase 1 criteria). Furthermore, an increase in antitumor humoral immune response was seen in some patients. However, a demonstration of clinical effectiveness of direct injection of copy mRNA for antitumor immunotherapy was not shown in this study and must be evaluated in subsequent trials.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1524-9557
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
180-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18481387-Adult, pubmed-meshheading:18481387-Aged, pubmed-meshheading:18481387-Antibody Formation, pubmed-meshheading:18481387-Antigens, Neoplasm, pubmed-meshheading:18481387-CD4-Positive T-Lymphocytes, pubmed-meshheading:18481387-CD8-Positive T-Lymphocytes, pubmed-meshheading:18481387-Cancer Vaccines, pubmed-meshheading:18481387-Cell Line, Tumor, pubmed-meshheading:18481387-Female, pubmed-meshheading:18481387-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:18481387-Humans, pubmed-meshheading:18481387-Immunity, Cellular, pubmed-meshheading:18481387-Injections, Intradermal, pubmed-meshheading:18481387-Interferon-gamma, pubmed-meshheading:18481387-Male, pubmed-meshheading:18481387-Melanoma, pubmed-meshheading:18481387-Middle Aged, pubmed-meshheading:18481387-Monitoring, Immunologic, pubmed-meshheading:18481387-Neoplasm Metastasis, pubmed-meshheading:18481387-Neoplasm Staging, pubmed-meshheading:18481387-RNA, Messenger, pubmed-meshheading:18481387-Treatment Outcome
pubmed:articleTitle
Results of the first phase I/II clinical vaccination trial with direct injection of mRNA.
pubmed:affiliation
Department of Dermatology, Institute for Cell Biology, University of Tübingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Clinical Trial, Phase II, Clinical Trial, Phase I