The safety of multiple antigen stimulating cellular therapy in treating patients with hepatocellular carcinoma
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Abstract:
Objective:To evaluate the safety of multiple antigen stimulating cellular therapy (MASCTTM) in treating patients with hepatocellular carcinoma (HCC). Methods: The clinical datas of 45 HCC patients, who received MASCTTM from January 2012 to December 2014 in the Center of Liver Diseases of Nanfang Hospital, were retrospectively analyzed. These patients did not receive any other immunotherapy before and their latest treatment (surgery,radiotherapy or chemotherapy) was at least one month before receiving MASCTTM. Peripheral blood mononuclear cells (PBMCs) were separated on Day 0,and the adherent cells were induced into mature dendritic cells (mDCs) to load 14 types of antigen peptides, a small part of mDCs was injected intracutaneously into the area of inguinal lymph nodes on Day 8. The un-adherent cells were co-cultured with mDC on Day 7 and induced into cytotoxic T lymphocytes (CTLs); the quality of DCs and CTLs was controlled before injected intravenously into patients on Day 26. The adverse effects, blood routine examination results, and functional changes of liver and kidney were recorded after injection. Results: In mDCs, the percentage of CD80+, CD83+, CD86+ and HLA-DR+ was (98.5±5)%, (88.0±10)%, (98.4±3)%, and (98.8±2)%, respectively; mDC secreted high level of IL-12(985±312) pg/ml and low level of IL-10(53±10) pg/ml. The percentage of CD3+CD8+ and CD3+CD56+ cells in CTLs was (83.0±10)% and (24.0±5)%, respectively; CTL secreted high level of IFN-γ (1 222±650) pg/ml and low level of IL-10(7±5) pg/ml. Most of the 45 patients had alleviation in appetite, sleep and physical condition after MASCTTM treatment. There were 2 patients (4.4%) had moderate fever after infusion with CTLs, but without other severe adverse reactions. There was no significant difference in renal function or blood routine examination before and after treatment. But ATL, AST, TBIL in liver function were increased a little.Conclusion: MASCTTM induced mDC and CTL successfully; it is a feasible treatment for HCC patients with less adverse effects and good clinical safety.
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Project supported by the National Natural Science Foundation for Young Scientists of China (No. 81502378), and the Technological Innovation and Venture Capital Project of Shenzhen City (No.CYZZ20140421141521053)