Cytostatic and immunomobilizing activities of polymer-bound drugs: experimental and first clinical data
Language English Country Netherlands Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
12932633
DOI
10.1016/s0168-3659(03)00235-9
PII: S0168365903002359
Knihovny.cz E-resources
- MeSH
- Antibiotics, Antineoplastic administration & dosage pharmacology therapeutic use MeSH
- Antineoplastic Agents administration & dosage pharmacology therapeutic use MeSH
- Killer Cells, Lymphokine-Activated drug effects MeSH
- Killer Cells, Natural drug effects MeSH
- Adult MeSH
- Doxorubicin administration & dosage pharmacology therapeutic use MeSH
- Enzyme-Linked Immunosorbent Assay MeSH
- Immunoglobulin G administration & dosage pharmacology therapeutic use MeSH
- Immunoglobulins chemistry MeSH
- Liver Function Tests MeSH
- Blood Cell Count MeSH
- Middle Aged MeSH
- Humans MeSH
- Mastectomy MeSH
- Methacrylates chemical synthesis chemistry MeSH
- Antibodies, Monoclonal pharmacology MeSH
- Mice MeSH
- Tumor Cells, Cultured MeSH
- Breast Neoplasms drug therapy surgery MeSH
- Polymers MeSH
- Excipients MeSH
- Thymidine metabolism MeSH
- Animals MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antibiotics, Antineoplastic MeSH
- Antineoplastic Agents MeSH
- Doxorubicin MeSH
- hydroxypropyl methacrylate MeSH Browser
- Immunoglobulin G MeSH
- Immunoglobulins MeSH
- Methacrylates MeSH
- Antibodies, Monoclonal MeSH
- Polymers MeSH
- Excipients MeSH
- Thymidine MeSH
An N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carrier containing doxorubicin and human immunoglobulin as an actively/passively targeting moiety was used in four patients with generalized breast cancer resistant to standard cytotoxic chemotherapy. The dose and time schedule were deduced from a Phase I clinical trial in which doxorubicin bound to HPMA copolymer carrier (PK1) was tested. It was confirmed that the Dox-HPMA-HuIg conjugate is stable and doxorubicin remains in the peripheral blood with a small amount also in the urine, mostly in its polymer-bound form. More than 116 biochemical, immunological and hematological parameters were determined for blood samples taken from patients 24 h, 48 h, 72 h and 1 to 11 weeks after treatment. Depending on the patient, some parameters decreased permanently or temporarily to the normal level (CRP, C3, CA 72-4, beta(2)-microglobulin, ferritin, CEA, CA 125, CD4, CD8, CE19, CD16(+)56(+), leu, ery) and some moved markedly towards physiological values (AST, ALT, ALP, GMT, CA 15-3, NSE, AFP). While the number of peripheral blood reticulocytes was significantly decreased after treatment with the classical free drug, their number was not affected or was even elevated after treatment with Dox-HPMA-HuIg. Increased absolute numbers of CD16(+)56(+) and CD4(+) cells in the peripheral blood and activation of NK and LAK cells in all patients support data obtained in experimental animals, pointing to a dual, i.e. cytostatic and immunomobilizing character of Dox-HPMA conjugates containing a targeting immunoglobulin moiety.
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