title: Chemotherapy based on HPMA copolymer conjugates with pH-controlled release of doxorubicin triggers anti-tumor immunity.
abstract: A novel class of anti-cancer therapeutics - polymeric conjugates of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers and doxorubicin with pH-controlled release of the drug - is highly efficient in killing tumor cells in vitro and is potent in eradicating growing tumors in vivo. Moreover, in comparison with low-molecular-weight drugs, the macromolecular therapeutics show decreased acute as well as delayed adverse side-toxicity. More importantly, the polymeric conjugates trigger the onset of specific anti-tumor immune response and this anti-tumor immunity can be transferred with splenocytes to naïve recipients. In other terms, chemotherapy based on conjugates of HPMA copolymer with doxorubicin possesses immunomodulating properties. This finding might also have wider implications for the management of relapsing tumors in human patients.
authors.affiliation: Department of Immunology and Gnotobiology, Institute of Microbiology ASCR, Prague, Czech Republic. mrkvan@biomed.cas.cz
authors.forename: Tomas
authors.initials: T
authors.lastname: Mrkvan
authors.forename: Milada
authors.initials: M
authors.lastname: Sirova
authors.forename: Tomas
authors.initials: T
authors.lastname: Etrych
authors.forename: Petr
authors.initials: P
authors.lastname: Chytil
authors.forename: Jiri
authors.initials: J
authors.lastname: Strohalm
authors.forename: Dana
authors.initials: D
authors.lastname: Plocova
authors.forename: Karel
authors.initials: K
authors.lastname: Ulbrich
authors.forename: Blanka
authors.initials: B
authors.lastname: Rihova
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D005688:Galactosamine / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016219:Immunotherapy, Adoptive; D020128:Inhibitory Concentration 50; D007279:Injections, Subcutaneous; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control*; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation
chemical_list: D000178:Acrylamides; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; C438845:HPMA coploymer-doxorubicin-galactosamine; D011109:Polymethacrylic Acids; C055176:doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate; D005688:Galactosamine; D004317:Doxorubicin