ABSTRACT
Objective:To investigate whether human umbilical vein endothelial cell(HUVEC) vaccine combined with low dose docetaxel (DOC) could play a synergistic role in anti-breast cancer.Methods:BALB/c mice were randomly divided into normal saline group,HUVEC vaccine group,DOC group,and HUVEC vaccine combined with DOC treatment group (HUVEC-DOC) group.An experimental metastasis model by tail vein injection of EMT-6 breast cancer cells was employed to evaluate the anti-metastatic efficiency of the HUVEC-DOC combination treatment regime.Lymphocyte proliferation assay,cytotoxic T lymphocytes and an indirect enzyme-linked immunosorbent assay (ELISA) for detecting IFN-γ were used to investigate cellular immune responses elicited by the combination treatment regime.Results:Compared with HUVEC and DOC single drug group,the number of lung metastasis in HUVEC-DOC combination treatment group was significantly decreased(P<0.05).In vitro analysis of splenocytes isolated from immunized mice revealed an induction of cytotoxic T lymphocytes(CTLs) with a lytic activity against activated endothelium.IFN-γ in the serum of im-munized mice of the HUVEC-DOC combination treatment group was significantly higher than that in the other three groups(P<0.05). Conclusion:HUVEC vaccine with low dose of DOC could display synergistic anti-breast cancer effect.
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.