Methods for inhibiting antigen specific t cell responses

Details Methods for inhibiting antigen specific t cell responses Methods for inhibiting antigen specific t cell responses

A - Human Necessities

61

K

A61K 38/17 (2006.01) A61K 39/395 (2006.01) C07K 14/705 (2006.01) C07K 14/725 (2006.01) C07K 16/24 (2006.01) C07K 16/28 (2006.01) C07K 19/00 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2191733

Methods for inhibiting antigen-specific T cell responses by use of an agent which inhibits a costimulatory signal in T cells are disclosed. Preferably, both a first agent which inhibits a costimulatory signal in the T cell (e.g., a CTLA4Ig fusion protein) and a second agent which inhibits another T cell function, such as adhesion of the T cell to a cell presenting antigen to the T cell, are used to inhibit antigen-specific T cell responses. For example, to inhibit adhesion of a T cell to a cell presenting antigen, an anti-LFA-1 antibody can be used in conjunction with a CTLA4Ig fusion protein. Alternatively, another agent which inhibits a costimulatory signal in T cells, such as an anti-B7-1 antibody or an anti-B7-2 antibody can be used with a second agent which inhibits a proliferative signal in the T cell e.g., an anti- IL-2 receptor antibody. The methods of the invention are particularly useful for inhibiting graft versus host disease and for inhibiting rejection of a transplanted tissue or organ.

Procédés d'inhibition des réponses des lymphocytes T spécifiques à un antigène qui consistent à utiliser un agent qui inhibe un signal de co-stimulation dans les lymphocytes T. Afin d'inhiber les réponses des lymphocytes T spécifiques à un antigène, on utilise de préférence un premier agent qui inhibe un signal de co-stimulation dans le lymphocyte T (par exemple une protéine de fusion CTLA41g) ainsi qu~un deuxième agent qui inhibe une autre fonction du lymphocyte T, telle que l'adhésion du lymphocyte T à une cellule qui présente un antigène dirigié contre les lymphocytes T. Par exemple, pour inhiber l'adhésion d'un lymphocyte T à une cellule présentant un antigène, on peut utiliser un anticorps anti-LFA-1 associé à une protéine de fusion CTLA41g. De plus, on peut également utiliser un autre agent qui inhibe un signal de co-stimulation dans les lymphocytes T, tel qu'un anticorps anti-B7-1 ou un anticorps anti-B7-2, conjointement avec un deuxième agent qui inhibe un signal de prolifération dans le lymphocyte T, par exemple un anticorps du récepteur anti-IL-2. Ces procédés sont particulièrement utiles pour inhiber la réaction du greffon contre l'hôte et le rejet de tissus ou d'organes transplantés.

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