Back to Search
Start Over
Modulation of cancer cell survival pathways using multivalent liposomal therapeutic antibody constructs.
- Source :
-
Molecular cancer therapeutics [Mol Cancer Ther] 2007 Mar; Vol. 6 (3), pp. 844-55. Date of Electronic Publication: 2007 Mar 05. - Publication Year :
- 2007
-
Abstract
- Various methods have been explored to enhance antibody-based cancer therapy. The use of multivalent antibodies or fragments against tumor antigens has generated a great deal of interest, as various cellular signals, including induction of apoptosis, inhibition of cell growth/survival, or internalization of the surface molecules, can be triggered or enhanced on extensive cross-linking of the target/antibody complex by the multivalent form of the antibody. The goal of the studies reported here was to develop multivalent antibody constructs via grafting of antibody molecules onto liposome membranes to enhance antibody activity. Using trastuzumab and rituximab as examples, up to a 25-fold increase in the antibody potency in cell viability assay was observed when the antibodies were presented in the multivalent liposome formulation. Key cell survival signaling molecules, such as phosphorylated Akt and phosphorylated p65 nuclear factor-kappaB, were down-regulated on treatment with multivalent liposomal trastuzumab and liposomal rituximab, respectively. Potent in vivo antitumor activity was shown for liposomal trastuzumab. The data presented here showed the potential of liposome technology to enhance the therapeutic effect of antibodies via a mechanism that modulates cell survival through clustering of the target/antibody complex.
- Subjects :
- Animals
Antibodies, Monoclonal, Humanized
Antibodies, Monoclonal, Murine-Derived
Antibodies, Neoplasm
Antigens, CD20 immunology
Antigens, Neoplasm immunology
Blotting, Western
Breast Neoplasms immunology
Breast Neoplasms pathology
Cell Survival
DNA-Binding Proteins genetics
DNA-Binding Proteins physiology
Down-Regulation
Female
Flow Cytometry
Genes, erbB-2 genetics
Genes, erbB-2 immunology
Humans
Liposomes
Mice
Mice, Knockout
Phosphorylation
Proto-Oncogene Proteins c-akt metabolism
Receptor, ErbB-2 immunology
Rituximab
Signal Transduction
Transcription Factor RelA metabolism
Trastuzumab
Antibodies, Monoclonal administration & dosage
Antineoplastic Agents administration & dosage
Breast Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1535-7163
- Volume :
- 6
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular cancer therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 17339368
- Full Text :
- https://doi.org/10.1158/1535-7163.MCT-06-0159