ABSTRACT
Cancer cell vaccine-based immunotherapy has received increasing interest in many clinical trials involving patients with breast cancer. Combining with appropriate adjuvants can enhance the weak immunogenic properties of tumor cell lysates (TCL). In this study, diphtheria toxin (DT) and two tandem repeats of mycobacterial heat shock protein 70 (mHSP70) fragment 407-426 (M2) were conjugated to TCL with glutaraldehyde, and the constructed cancer cell vaccine was named DT-TCL-M2. Subcutaneous injection of DT-TCL-M2 in mice effectively elicited tumor-specific polyclonal immune responses, including humoral and cellular immune responses. High levels of antibodies against TCL were detected in the serum of immunized mice with ELISA and verified with Western blot analyses. The splenocytes from immunized mice showed potent cytotoxicity on Ehrlich ascites carcinoma cells. Moreover, the protective antitumor immunity induced by DT-TCL-M2 inhibited tumor growth in a mouse breast tumor model. DT-TCL-M2 also attenuated tumor-induced angiogenesis and slowed tumor growth in a mouse intradermal tumor model. These findings demonstrate that TCL conjugated with appropriate adjuvants induced effective antitumor immunity in vivo. Improvements in potency could further make cancer cell vaccines a useful and safe method for preventing cancer recurrence after resection.
Subject(s)
Animals , Female , Mice , Adjuvants, Immunologic , Bacterial Proteins , Genetics , Allergy and Immunology , Cancer Vaccines , Allergy and Immunology , Carcinoma, Ehrlich Tumor , Allergy and Immunology , Pathology , Cell Line, Tumor , Cell Proliferation , Diphtheria Toxin , Genetics , Allergy and Immunology , HSP70 Heat-Shock Proteins , Genetics , Allergy and Immunology , Immunoglobulin G , Allergy and Immunology , Immunotherapy , Neovascularization, Pathologic , Peptide Fragments , Genetics , Allergy and Immunology , Recombinant Fusion Proteins , Genetics , Allergy and Immunology , T-Lymphocytes, Cytotoxic , Allergy and Immunology , Tandem Repeat SequencesABSTRACT
Although the effect of mouse resistin on insulin-resistance has been well defined, but the biological function of human resistin is still unknown. This study was aimed to explore the possible physiological and pathological effects of human resistin, as well as the tissue distribution of human resistin and correlation of resistin gene expression with leukemia incidence. 152 leukemia patients without inflammatory complication and 100 healthy persons were selected as experimental and control groups respectively. The blood samples were collected, the total RNA was extracted, the expression distribution of resistin in different tissues was detected by semi-quantitative RT-PCR and then the statistical analysis was carried out. The results indicated that the expression of the human resistin gene was detected in normal fetus liver, adult bone marrow and umbilical cord blood and peripheral blood cells, while the resistin gene could not be amplified in fat, umbilical cord, placenta and adult liver. The resistin expression was detected in 21% leukemia patients and 27% healthy persons. The difference of the resistin gene expression between the two groups was not statistically significant (p>0.05). It is concluded that the higher expression of resistin exists in normal human fetus liver, adult bone marrow, umbilical cord blood and peripheral blood cells, which indicates that the distribution of human resistin correlates with normal hematopoiesis in certain extent, but its expression level and rate may not correlate with the incidence of leukemia.