Cytostatic and immunomobilizing activities of polymer-bound drugs: experimental and first clinical data

J Control Release. 2003 Aug 28;91(1-2):1-16. doi: 10.1016/s0168-3659(03)00235-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacology*
  • Antibiotics, Antineoplastic / therapeutic use
  • Antibodies, Monoclonal / pharmacology
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Blood Cell Count
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / surgery
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacology*
  • Doxorubicin / therapeutic use
  • Enzyme-Linked Immunosorbent Assay
  • Excipients
  • Female
  • Humans
  • Immunoglobulin G / administration & dosage
  • Immunoglobulin G / pharmacology*
  • Immunoglobulin G / therapeutic use
  • Immunoglobulins / chemistry
  • Killer Cells, Lymphokine-Activated / drug effects
  • Killer Cells, Natural / drug effects
  • Liver Function Tests
  • Mastectomy
  • Methacrylates / chemical synthesis
  • Methacrylates / chemistry*
  • Mice
  • Middle Aged
  • Polymers
  • Thymidine / metabolism
  • Tumor Cells, Cultured


  • Antibiotics, Antineoplastic
  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Excipients
  • Immunoglobulin G
  • Immunoglobulins
  • Methacrylates
  • Polymers
  • Doxorubicin
  • hydroxypropyl methacrylate
  • Thymidine