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5. Assessing the potential of hypochlorous acid-oxidised allogenic tumour cells as a source of antigen for dendritic cell-based immunotherapy of ovarian carcinoma

Author

Chiang, C. L. L.

Subjects
617
Abstract

Ovarian cancer commonly relapses after remission and activating tumour-specific T cells with dendritic cells loaded with tumour cells is a promising approach to target residual microscopic tumours. SK-OV-3 cells expressing HER-2/neu and MUC1 ovarian antigens were killed and their immunogenicity enhanced by hypochlorous acid (HOC1) oxidation. Treatment with 60 uM HOC1 for 1 h induced necrosis in all the cells. Oxidised, but not live SK-OV-3 were engulfed by monocyte-derived DCs. Autologous T cells primed with DCs of HLA-A2+ healthy volunteers loaded with oxidised SK-OV-3 (HLA-A2") recognised oxidised SK-OV-3 and HLA-A2-restricted epitopes of MUC1 and HER-2/neu. Responses were absent with heat- or hydrochloric acid (HCl)-killed SK-OV-3, thus HOC1 oxidation and not cell death/necrosis enhanced the immunogenicity of SK-OV-3. Oxidised SK-OV-3 primed T cells did not respond to oxidised melanoma, or vice versa. Next, T cells of ovarian cancer patients in remission, whose tumours overexpressed MUC1 and/or HER-2/neu, were tested using the same model. DCs of HLA-A2+ and A2" patients pulsed with oxidised SK- OV-3 stimulated T cells specific for oxidised SK-OV-3, and HER-2/neu and MUC1 epitopes. Oxidised SK-OV-3 loaded DCs further matured with CD40 agonistic antibody or monophosphoryl lipid A, primed stronger CD4+ and CD8+ responses than immature DCs. T cells stimulated this way also recognised autologous tumour cells from ascites, demonstrating that SK-OV-3 shared significant antigenic repertoire with tumours in patients. Finally, this DC-based vaccination was tested in vivo using the B16.F10 melanoma model. B16.F10 highly expressed tyrosinase-related protein (TRP)-2, and all the cells were necrotic after 1 h treatment with 60uM HOC1. Mice immunised intravenously and not intraperitoneally or subcutaneously with bone- marrow derived DCs loaded with oxidised B16.F10, responded to TRP-2 and oxidised B16.F10. Oxidised and not heat- or HCl-killed B16.F10, primed specific T cells in vivo. DCs were required for efficient delivery for processing and presentation of oxidised B16.F10 in vivo.

Published
2008

38. Drying Kinetics and Modelling of Convective Drying of Kedondong Fruit.

Author

Ee, C. T., Khaw, Y. J., Hii, C. L., Chiang, C. L., and Djaeni, M.

Subjects
DRIED fruit, FRUIT drying, NONLINEAR regression, ACTIVATION energy, FRUIT, SNACK foods
Abstract

Kedondong is an underutilized fruit cultivated in a small scale in Malaysia and it contains nutrients that can be preserved through drying. The dried product can be sold as a premium fruit snack that could generate revenue for the producer. We studied the drying of peeled and unpeeled kedondong fruits using hot air (60-80°C). This study aims to investigate the drying kinetics (drying rates and effective diffusivities) of kedondong fruits and model the drying curves using thin layer models. Ten thin layer models were employed and solved using non-linear regression. Drying kinetics showed that only falling rate periods were observed, which implied that internal diffusion was the dominant mechanism for moisture release. Mathematical models showed that Modified Hii et al. (I) and (II) models were able to predict the drying curve well with the highest R² (0.9992-0.9999), the lowest RMSE (8.0 x 10-4 - 2.5 x 10-3) and the lowest X² (4.0 ×10-5 - 2.0 x 10-4). Peeled samples showed higher effective diffusivities (average 3.2 x 10-11 m²/s) than unpeeled samples (average 2.7 x 10-11 m²/s). The activation energy was lower in peeled samples (25.8 kJ/mol) as moisture diffusion could occur more easily than unpeeled samples (32.1 kJ/mol). Results from this study provide kinetic information that can be used in scaling up of dryer and optimizing dryer performances. [ABSTRACT FROM AUTHOR]

Published
2021
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46. Kombinierte stereotaktische Körperstamm-Strahlentherapie und transarterielle Chemoembolisation als Erstlinientherapie beim hepatozellulären Karzinom im BCLC-Stadium B–C.

Author

Chiang, C. L., Chan, Mark K. H., Yeung, Cynthia S. Y., Ho, Connie H. M., Lee, Francis A. S., Lee, Venus W. Y., Wong, Frank C. S., and Blanck, Oliver

Abstract

Purpose: We retrospectively evaluated the efficacy and safety of stereotactic body radiotherapy (SBRT) combined with trans-arterial chemoembolization (TACE) as initial therapy in Barcelona Clinic Liver Cancer (BCLC) system stage B-C hepatocellular carcinoma (HCC).Patients and Methods: Seventy-two patients received a single dose of TACE followed by SBRT 4 weeks later. All patients had tumor sizes ≥5 cm, at least 700 ml of disease-free liver, Child-Pugh (CP) score ≤ B7 and tumor nodules ≤5. SBRT dose, ranging from 6 × 5-8 Gy or 5-10 × 4 Gy, was individualized according to normal tissue constraints. No subsequent scheduled treatment was delivered unless disease progression was observed. Local control (LC), overall survival (OS), progression-free survival (PFS), response rate (RR), and toxicity were evaluated.Results: The patients' characteristics were: median age 60 years (range 28-87 years); CP score A/B (n = 68/4); BCLC stage B/C (n = 51/21); solitary/multifocal (n = 37/35); portal vein invasion (n = 18). The median tumor size and GTV were 11.2 cm (range 5.0-23.6 cm) and 751 cm3 (range 41-4009 cm3), respectively. The median equivalent dose in 2 Gy per fraction (EQD2, α/β = 10) was 37.3 Gy2 (range, 28-72 Gy2). The median follow-up time was 16.8 months (range, 3-96 months). The objective RR was 68% and the 1‑year LC rate was 93.6% (95% CI, 87.6-100%). The median OS was 19.8 months (95% CI, 11.6-30.6 months). SBRT-related grade 3 or higher adverse gastrointestinal events and treatment-related death occurred in three (2.8%) and one patient (1.4%) respectively. No patient developed classical radiation-induced liver injury.Conclusion: Our experience suggests that combined TACE and SBRT can be a safe and effective initial therapy for BCLC stage B-C HCC with appropriate patient selection. Further prospective trials are warranted. [ABSTRACT FROM AUTHOR]

Published
2019
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