Doxorubicin plus interleukin-2 chemoimmunotherapy against breast cancer in mice.

Abstract:

: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.

journal_name

Cancer Res

journal_title

Cancer research

authors

Ewens A,Luo L,Berleth E,Alderfer J,Wollman R,Hafeez BB,Kanter P,Mihich E,Ehrke MJ

doi

10.1158/0008-5472.CAN-05-3963

subject

Has Abstract

pub_date

2006-05-15 00:00:00

pages

5419-26

issue

10

eissn

0008-5472

issn

1538-7445

pii

66/10/5419

journal_volume

66

pub_type

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