Chemotherapy based on HPMA copolymer conjugates with pH-controlled release of doxorubicin triggers anti-tumor immunity.
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.
Mrkvan
Tomas
T
Department of Immunology and Gnotobiology, Institute of Microbiology ASCR, Prague, Czech Republic. mrkvan@biomed.cas.cz
Sirova
Milada
M
Etrych
Tomas
T
Chytil
Petr
P
Strohalm
Jiri
J
Plocova
Dana
D
Ulbrich
Karel
K
Rihova
Blanka
B
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
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