Details

Autor(en) / Beteiligte

• Aldouri, Amer Qais Ibrahim

Titel

Tumour lysate-loaded dendritic cells for the immunotherapy of cancer

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2007

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• The aim of this thesis was to optimise tumour lysates preparation for immunotherapy in an autologous model of colorectal liver metastases, to load DC with the optimised lysates and to look at a range of approaches to enhance the immunogenicity of such vaccines. Tumour lysates were prepared by different methods from resected colorectal liver metastases. The impact of each tumour lysates preparation on DC and their response to maturation factors was assessed in terms of DC phenotype (expression of CD80, CD86 and MHC11) and their cytokines production (IL-12p70 and IL-10). Whole tumour lysates preparation was shown to inhibit DC response to maturation factors, both in allergenic and autologous setting. This inhibition was completely released with centrifugation or filtration of tumour lysates. We also demonstrated uptake of lysates protein by DC from the centrifuged lysate; furthermore we optimised a protein concentration range for pulsing DC without adversely affecting their function. Stressing of tumour tissue with heat or irradiation prior to lysates preparation showed no enhancement to the immunogenicity of the lysates in terms of DC maturation. However, lysates prepared from tumour tissue injected with oncolytic virus (reovirus) was shown to have increased immunogenicity. In conclusion, we have characterised an optimal method for tumour lysates/DC vaccine preparation in our clinically relevant model and have shown that these vaccines may be more immunogenic by the addition of a viral adjuvant.