Abstract
Over the last two decades, dendritic cell (DC) vaccination has been studied extensively as active immunotherapy in cancer treatment and has been proven safe in all clinical trials both with respect to short and long-term side effects. For antigen-loading of dendritic cells (DCs) one method is to introduce mRNA coding for the desired antigens. To target the whole antigenic repertoire of a tumor, even the total tumor mRNA of a macrodissected biopsy sample can be used. To date, reports have been published on a total of 781 patients suffering from different tumor entities and HIV-infection, who have been treated with DCs loaded with mRNA. The majority of those were melanoma patients, followed by HIV-infected patients, but leukemias, brain tumors, prostate cancer, renal cell carcinomas, pancreatic cancers and several others have also been treated. Next to antigen-loading, mRNA-electroporation allows a purposeful manipulation of the DCs’ phenotype and function to enhance their immunogenicity. In this review, we intend to give a comprehensive summary of what has been published regarding clinical testing of ex vivo generated mRNA-transfected DCs, with respect to safety and risk/benefit evaluations, choice of tumor antigens and RNA-source, and the design of better DCs for vaccination by transfection of mRNA-encoded functional proteins.
Highlights
Therapeutic cancer vaccination is a concept for treating tumor patients by immunizing them against their own tumor
Reports have been published on a total of 781 patients suffering from different tumor entities and HIV-infection, who have been treated with dendritic cell (DC) loaded with mRNA
The mammalian cell type which is specialized in initiating all adaptive immune responses was described in 1973 by Ralph Steinman and Zanvil Cohn and termed dendritic cells (DCs) [7]
Summary
Therapeutic cancer vaccination is a concept for treating tumor patients by immunizing them against their own tumor. As early as 1891, the application of bacterial substances (which we know to have served as adjuvants) into tumors was executed by William Coley, who achieved a clinical response rate of 10% in soft tissue sarcoma [1,2]. During the 20th century, chemotherapy and radiation therapy were developed and superseded immunotherapy. The concept of immune surveillance, was later resumed and pursued [3,4] (and reviewed by [5,6]). The striking success that was achieved in preventive vaccination against infectious diseases suggested that the immune system could be utilized against malignancies in a similar fashion
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