Antigen-specific T cell–mediated gene therapy in collagen-induced arthritis

Vectors for the treatment of autoimmune disease

“…78 Collagen II-specific T-cell hybridomas modified to express an IL-12 antagonist were capable of ameliorating CIA. 79 Adoptive transfer of syngeneic B cells, transduced by fusion genes of autoantigens with IgG1 H chain, 80 or with lysosome-targeting Lamp-1 signal, 81 prevent and even cure animal models of diabetes and MS. Fibroblasts and arthritogenic splenocytes transduced to express soluble complement receptor 1 were therapeutic in mouse CIA. 82 Indeed, ex vivo retroviral strategies have already entered the clinic.…”

“…The most straightforward is local delivery of transducing agent or of ex vivo transduced cells. Other approaches include: employment of tissue-specific homing of ex vivo transduced cells, for example, T cells, 79,132 introduction of tissue-specific promoters and enhancers and finally, modification of the tropism of viral particles, so that only cells expressing particular surface markers are transduced. Of these strategies, only the latter two deal directly with vectors themselves and will be considered here.…”

Celiac Disease: a model autoimmune disease with gene therapy applications

“…As discussed above collagen type II and Myelin Basic Protein-specific T cells or genetically engineered T/B 55 cells have been used for this purpose. 10,11 In CD, we would have a dual benefit in using antigen (gliadin)-specific T cells as these T cells tend to localize at the site of the lesion (small intestine). Moreover, since they are pathogenic, they also represent the ideal cells to be targeted.…”

“…In this scenario, a lymphocyte (normally a T lymphocyte) with the antigenic specificity for a self antigen, regardless of the potential significance of this autoantigen as trigger of the autoimmune disease, is located at the site of autoimmune inflammatory reaction. Examples of antigens that have been used in animal models are Collagen type II in collagen-induced arthritis, an animal model of rheumatoid arthritis, 10,11 and myelin basic protein in EAE 12 an animal model of multiple sclerosis. In this scenario, the self-antigen specificity is used as an ideal homing devise to localize cells that have been transduced to secrete powerful anti-inflammatory substances, often cytokines (such as IL-10) or cytokines receptors (such as soluble TNF receptor).…”

Collagen II-pulsed antigen-presenting cells genetically modified to secrete IL-4 down-regulate collagen-induced arthritis

“…14 Indeed, several groups reported the successful localization of the transgene in the inflamed tissues associated with reversion of pathological manifestations in different murine models of autoimmunity, including CIA, by injection of antigen-specific T cells transduced with retroviral vectors encoding for IL-4, 15 IL-10 16,17 , TGF-␤ 18 or IL-12 antagonist. 19 Most recent strategies pointed to immunosuppressive capacities of Gene Therapy antigen-presenting cells (APC) engineered to express regulatory proteins. 20 For example, APC expressing high levels of Fas ligand down-modulated pathological signs in a murine model of chronic inflammatory disease.…”