ABSTRACT
PURPOSE: Various tumor antigens can be loaded onto dendritic cells (DCs) to induce a potent cytotoxic T lymphocyte (CTL) response in DC-based immunotherapy against breast cancer. However, in the clinical setting, obtaining a sufficient number of autologous tumor cells as a source of tumor antigens is a laborious process. We therefore investigated the feasibility of immunotherapy using breast-cancer-specific CTLs generated in vitro by use of alpha-type 1 polarized DCs (alpha DC1s) loaded with ultraviolet B-irradiated cells of the breast cancer cell line MCF-7. MATERIALS AND METHODS: alphaDC1s were induced by loading allogeneic tumor antigen generated from the MCF-7 UVB-irradiated breast cancer cell line. Antigen-pulsed alphaDC1s were evaluated by morphological and functional assays, and the breast-cancer-specific CTL response was analyzed by cytotoxic assay. RESULTS: The alphaDC1s significantly increased the expression of several molecules related to DC maturation without differences according to whether the alphaDC1s were loaded with tumor antigens. The alphaDC1s showed a high production of interleukin-12 both during maturation and after subsequent stimulation with CD40L, which was not significantly affected by loading with tumor antigens. Breast-cancer-specific CTLs against autologous breast cancer cells were successfully induced by alphaDC1s loaded with apoptotic MCF-7 cells. CONCLUSION: Autologous DCs loaded with an allogeneic breast cancer cell line can generate potent breast-cancer-specific CTL responses. This may be a practical method for cellular immunotherapy in patients with breast cancer.
Subject(s)
Humans , Antigens, Neoplasm , Breast , Breast Neoplasms , CD40 Ligand , Cell Line , Dendritic Cells , Immunotherapy , Interleukin-12 , Lymphocytes , T-Lymphocytes, CytotoxicABSTRACT
BACKGROUND: It is often difficult to make a diagnosis of cardiac ischemia in patients attending emergency department (ED) with symptoms of acute coronary syndromes (ACS) because existing cardiac markers are not sensitive for reversible myocardial ischemia. Ischemia modified albumin (IMA) has recently been shown to be an early and sensitive marker of myocardial ischemia. We investigated the usefulness of ischemia modified albumin (IMA) as an early triage marker for ACS and tried to establish a newly standardized albumin-adjusted IMA index which has been expected to be more sensitive and accurate than conventional IMA value. METHODS: We enrolled 209 consecutive patients (men 95, women 114) who presented to the ED with symptoms suggestive of ACS from June to July, 2005. All patients were classified to ACS group (n=42) and others (n=167) based on diagnosis of cardiologists. The ideal cutoff value of IMA was calculated by the receiver operating characteristic (ROC) curve analysis and diagnostic utilities of combination tests (myoglobin, CK-MB, troponin T and EKG) were compared with those of IMA. The albumin-adjusted IMA index was calculated and applicated from the results of correlation assay between serum albumin concentration and IMA value. RESULTS: Mean IMA level (U/mL) of ACS group was significantly higher than that of non-ACS group (P<0.05) and sensitivity and specificity was 92.9% and 35.9% at a cutoff value of 85.1 U/mL, respectably. In combination with conventional cardiac markers, the sensitivity increased to 96.3%. IMA value had a negative lnear relationship with serum albumin concentration (YIMA= -23.1Xalbumin+200, R=0.99) and albumin-adjusted IMA index was calculated as [IMA index = serum albumin conc. (g/dL) x 23 + IMA (U/mL) -100]. The sensitivity and specificity was 97.6% and 34.1% at a cutoff value of 83.3 IMA index, respectively. CONCLUSIONS: IMA is a useful sensitive marker for the identification of ACS in patients with normal cardiac markers and EKG finding and follow-up combination testing may be required to rule out other diseases. The calculated albumin-adjusted IMA index is recommended to make a diagnosis of ACS more sensitively.