RNA-transfected dendritic cells in cancer immunotherapy

DA Mitchell, SK Nair - The Journal of clinical investigation, 2000 - Am Soc Clin Investig
DA Mitchell, SK Nair
The Journal of clinical investigation, 2000Am Soc Clin Investig
1066 The Journal of Clinical Investigation| November 2000| Volume 106| Number 9 of
specific tumor antigens or that rely on the availability of abundant tumor tissue (cellular
extracts or apoptotic bodies) are applicable to very few cancer patients. While continued
advances in antigen discovery and tissue culture technique may alleviate these difficulties
and allow broader use of immunotherapies based on defined antigens, alternative
approaches will be needed for the foreseeable future. Nucleic acid transfection, which relies …
1066 The Journal of Clinical Investigation| November 2000| Volume 106| Number 9 of specific tumor antigens or that rely on the availability of abundant tumor tissue (cellular extracts or apoptotic bodies) are applicable to very few cancer patients. While continued advances in antigen discovery and tissue culture technique may alleviate these difficulties and allow broader use of immunotherapies based on defined antigens, alternative approaches will be needed for the foreseeable future. Nucleic acid transfection, which relies on well-characterized methods of cDNA cloning and amplification, allows for the antigenic content of tumors to be isolated from a small number of tumor cells (12). In fact, a cDNA library can be made from even a single cell, allowing the content of tumor cells to be isolated and amplified from nearly any cancer patient. The use of nucleic acid templates for the expression of tumor-derived antigens allows for the expression of the antigens as full-length proteins within DCs. This allows the antigen-processing machinery of the patients’ own DCs to process these proteins and display the peptides on their surface. A reasonable assumption is that the most relevant peptides are presented to the patient’s immune system. Vaccine strategies based on synthetic peptides or proteins require knowledge of the relevant peptides for that patient pool and assume that the peptides chosen will be the ones best recognized by the immune system of that patient. When DCs are transfected with the tumor antigens, the patient’s own immune system makes that choice. Thus, for both immunological and practical considerations, nucleic acid transfection of DCs offers several advantages over other described methods.
The Journal of Clinical Investigation
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