Best of AACR Journals

Cancer Prevention Research
Research Article
MUC1 Vaccine for Individuals with Advanced Adenoma of
the Colon: A Cancer Immunoprevention Feasibility Study
Takashi Kimura, John R. McKolanis, Lynda A. Dzubinski, Kazi Islam, Douglas M. Potter, Andres M. Salazar,
Robert E. Schoen, and Olivera J. Finn
Robert E. Schoen
Olivera J. Finn
Abstract
Cancer vaccines based on human tumor-associated antigens
(TAA) have been tested in patients with advanced or recurrent
cancer, in combination with or following standard therapy. Their
immunogenicity and therapeutic efficacy has been difficult to
properly evaluate in that setting characterized by multiple highly
suppressive effects of the tumor and the standard therapy on the
patient’s immune system. In animal models of human cancer,
vaccines administered in the prophylactic setting are most
immunogenic and effectively prevent cancer development and
progression. We report results of a clinical study that show that
in patients without cancer but with a history of premalignant
lesions (advanced colonic adenomas, precursors to colon cancer),
a vaccine based on the TAA MUC1 was highly immunogenic in
17 of 39 (43.6%) of vaccinated individuals, eliciting high levels of
anti-MUC1 immunoglobulin G (IgG) and long-lasting immune
memory. Lack of response in 22 of 39 individuals was correlated
with high levels of circulating myeloid-derived suppressor
cells (MDSC) prevaccination. Vaccine-elicited MUC1-specific
immune response and immune memory were not associated
with significant toxicity. Our study shows that vaccines based on
human TAAs are immunogenic and safe and capable of eliciting
long-term memory that is important for cancer prevention. We
also show that in the premalignant setting, immunosuppressive
environment (e.g., high levels of MDSC) might already exist in
some individuals, suggesting an even earlier premalignant stage or
preselection of nonimmunosuppressed patients for prophylactic
vaccination. Cancer Prev Res; 6(1); 18–26. ©2012 AACR.
Cancer Prev Res January 2013 6:18–26; Published OnlineFirst
December 17, 2012; doi:10.1158/1940-6207.CAPR-12-0275
Research Article
Increased Levels of Urinary PGE-M, a Biomarker of
Inflammation, Occur in Association with Obesity, Aging,
and Lung Metastases in Patients with Breast Cancer
Patrick G. Morris, Xi Kathy Zhou, Ginger L. Milne, Daniel Goldstein, Laura C. Hawks, Chau T. Dang,
Shanu Modi, Monica N. Fornier, Clifford A. Hudis, and Andrew J. Dannenberg
Patrick G. Morris
Andrew J. Dannenberg
Abstract
Elevated levels of COX-derived prostaglandin E 2 (PGE 2 ) occur
in inflamed tissues. To evaluate the potential links between
inflammation and breast cancer, levels of urinary prostaglandin E
metabolite (PGE-M), a stable end metabolite of PGE 2 , were quantified.
We enrolled 400 patients with breast cancer: controls with early breast
cancer (n = 200), lung metastases (n = 100), and metastases to other
sites (n = 100). Patients completed a questionnaire, provided urine,
and had measurements of height and weight. Urinary PGE-M was
quantified by mass spectrometry. Ever smokers with lung metastasis
who had not been exposed to nonsteroidal anti-inflammatory drugs
(NSAIDs) had the highest PGE-M levels. PGE-M levels were increased
in association with elevated body mass index (BMI; P < 0.001), aging
(P < 0.001), pack-year smoking history (P = 0.02), lung metastases
(P = 0.02), and recent cytotoxic chemotherapy (P = 0.03). Conversely,
use of NSAIDs, prototypic inhibitors of COX activity, was associated
with reduced PGE-M levels (P < 0.001). On the basis of the current
findings, PGE-M is likely to be a useful biomarker for the selection of
high-risk subgroups to determine the use of interventions that aim to
reduce inflammation and possibly the development and progression
of breast cancer, especially in overweight and obese women. Cancer
Prev Res; 6(5); 428–36. ©2013 AACR.
Cancer Prev Res May 2013 6:428–436; Published OnlineFirst March
26, 2013; doi:10.1158/1940-6207.CAPR-12-0431
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