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Archive > Volume 21 Issue 3 > 2014,21(3):237-244. DOI:10.3872/j.issn.1007-385X.2014.03.001 Prev Next
Prompt Report
Outcomes of patients with triple-negative breast cancer after vaccination with autologous dendritic cells loaded with apoptotic heat-shocked tumor antigen: Results from an multicenter randomized controlled clinical trial
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Abstract:
To assess the efficacy and safety profiles of vaccination with autologous DC loaded with apoptotic heat-shocked autologous tumor cell antigens in the treatment of triple-negative breast cancer (TNBC). Methods: A total of 168 patients with TNBC were recruited from three hospitals located, respectively, in Nanjing, Changzhou and Wuxi and randomized to a control group (n=56) and a treatment group (n=112). Patients in the treatment group were treated with DC vaccination for three cycles (one week each at an interval of one month) whereas those in the control group received placebo. The primary outcome measures were disease progression time (DPT) and progression-free survival rate (PFSR) at the end of 2-year follow up. The secondary outcome measures were side effects, tolerance to DC vaccination, tumor specific immune responses (i.e., changes in IL-2, IL-10, IL-12, TNF-α and IFN-γ concentrations）, the percentage of specific CD8+IFN-γ+T lymphocytes in peripheral blood and delayed type Ⅳ hypersensitivity reaction (DTH) before and after DC vaccinations. Results： No more than level Ⅱ side effects were observed in any of the participants. After one cycle of vaccination, there were significant and sustained increases in serum levels of Th1 type cytokines IL-2 (P=0038), TNF-α (P=0.024) and IFN-γ (P=0.022) in patients with stage I to stage Ⅲ lesions. The number of tumor-specific CD8+IFN-γ+T lymphocytes in the peripheral blood was increasing slowly and gradually over the course of vaccination therapy in patients with stage I to stage Ⅲ lesions; by the third cycle of DC vaccination the number became significantly higher as compared with the placebo (P<0.05). Overall, the rate of DTH was positively correlated with the vaccination cycle (r=0.973, P<0.05). When disease stages were compared, the rate of DTH was significantly higher in patients with stage I to stage Ⅲ disease than that in patients with stage Ⅳ lesions. The average DPT was 669 days in patients with stage Ⅰ to stage Ⅲ lesions and 656 days in stage Ⅳ patients in the treatment group, significantly longer than that in patients with stage I to stage Ⅲ (618 days) and stage Ⅳ (573 days) lesions in the control group (P<0.001). The average PFSR of stage Ⅲ and stage Ⅳ patients was 71.43% in the treatment group, but only 32.73% in the corresponding patients in the control group (P<0.001). Moreover, the average PFSR of DTH-positive patients was 87.30%, significantly higher than that of DTH-negative patients (51.02%). Conclusion: Autologous DC loaded with heat-shocked apoptotic autologous tumor cells may be effective in both eliciting the non-specific immune response of Th1 cells and tumor-specific CTL responses and delaying disease progression and improving survival in triple-negative breast cancer patients.
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Project Supported:
Project supported by the Key Foudation Project of the Health Bureau of Jiangsu Province (No.H200525); the Key Foudation Project of Nanjing Science and Technology Commission(No.201103058); the Science and Technology Plan Project of Changzhou City (No.CS2007215)
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