Doxorubicin plus interleukin-2 chemoimmunotherapy against breast cancer in mice.
As recently characterized, following s.c. implantation into syngeneic C57BL/6 mice, E0771 tumor invades locally into dermal layers and peritoneum, metastasizes to the lung, and induces a nonspecific immunosuppression in the host. Using this breast medullar adenocarcinoma model, a therapy consisting of a single moderate dose of doxorubicin followed by twice daily moderate doses of interleukin-2 for 30 days was examined for efficacy and mechanism of action when given to animals with established disease. This combination treatment, but not combinants alone, resulted in tumor-free long-term survival of 40% of the mice without significant toxicity and 83% of survivors had immune memory specific for E0771 cells. Treatment also decreased immune suppression induced by E0771 tumor. Full response to treatment required functional CD8(+) T cells, whereas depletion of natural killer cells caused only a reduction in response rate. A serum "biomarker" profile that correlated with, and seemed predictive of, response to treatment was identified by nuclear magnetic resonance-based metabonomic analysis. The efficacy of this nontoxic treatment and the potential to be able to predict which individual is responding to treatment are characteristics that make this chemoimmunotherapy attractive for clinical testing.
Ewens
Andrew
A
Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Luo
Liqun
L
Berleth
Erica
E
Alderfer
James
J
Wollman
Robert
R
Hafeez
Bilal Bin
BB
Kanter
Peter
P
Mihich
Enrico
E
Ehrke
M Jane
MJ
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity; D019008:Drug Resistance, Neoplasm; D005260:Female; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000008:administration & dosage / Q000633:toxicity; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
D007376:Interleukin-2; D004317:Doxorubicin