Klinische Pädiatrie
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Currently, several clinical studies explore the therapeutic potential of tumor vaccines which are genetically modified to produce immunostimulatory molecules as a complementary approach for conventional cancer therapy. In this review the immunological basis and the preclinical design of such vaccine strategies are described with particular emphasis to acute leukemia and neuroblastoma. The role of cytokines, chemokines and costimulatory surface molecules for generation of tumor vaccines is summarized, and the advantages and disadvantages of autologous, allogenic and dendritic cell vaccines are discussed. Finally, combination-immunogens are introduced as a potent means of enhancing the anti-tumor response.
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Klinische Pädiatrie · Jul 1999
ReviewFanconi anemia and beta c deficiency-associated pulmonary alveolar proteinosis as two hereditary diseases of childhood which are potentially curable by stem cell gene therapy but require different therapeutic approaches.
Fanconi anemia (FANC) and pulmonary alveolar proteinosis associated with deficiency of the beta-chain common to the GM-CSF/IL3/IL5 receptors (beta c-PAP) are rare inherited disorders of childhood or adolescence. Hematopoietic stem cell gene therapy aiming at reintroducing the wildtype cDNA as a new concept for the treatment of hereditary diseases may be applicable to FANC and PAP, as both disorders can be successfully treated by allogeneic stem cell transplantation. However, there are important distinctions to be made between the two diseases: FANC seems to be a disorder with functional stem cell deficiency. ⋯ The introduction of a second selectable cDNA into the vector might be used to provide selective growth for modified cells and thus overcome a low gene transfer efficiency of stem cells. The correction of rare monogenetic diseases may serve as a model for gene therapy prior to attempts to treat more common and complex polygenetic diseases. The studies outlined here will be helpful envisioning new treatment strategies for other inherited monogenetic diseases such as mucopolysaccharidosis, Gauchers disease or adrenoleukodystrophy.