Antisense oligomers and methods for inducing immune tolerance and immunosuppression

an antibody and immunosuppression technology, applied in the field of antibodies and immunosuppression, can solve the problems of immunosuppressive agents with severe side effects, high risk and drawbacks of allogeneic transplantation, and high debilitating or lethal side effects, so as to reduce the capacity for antigen-specific activation of t cells, enhance the expression of extracellular il-10, and increase the production of extracellular il-10
US20050234002A1Inactive Publication Date: 2005-10-20AVI BIOPHARMA
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Patent Information

Authority / Receiving Office
US · United States
Current Assignee / Owner
AVI BIOPHARMA
Publication Date
2005-10-20
Estimated Expiration
Not applicable · inactive patent

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Abstract

A method and composition for inducing human dendritic cells to a condition of reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10 is disclosed. A population of dendritic cells is exposed to a substantially uncharged antisense compound containing 12-40 subunits and a base sequence effective to hybridize to an expression-sensitive region of a preprocessed or processed human CD86 transcript identified, in its processed form, by SEQ ID NO:33, to form a duplex structure between said compound and transcript having a Tm of at least 45° C. Formation of the duplex blocks expression of full-length CD86 in said cells, which in turn leads to reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10.
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Description

[0001] This application claims priority to U.S. Provisional Application No. 60,538,655, filed Jan. 23, 2004, which is incorporated herein by reference in its entirety.FIELD OF THE INVENTION

[0002] The present invention relates to compounds and methods of inducing immunological tolerance using a peptide-antisense conjugate to selectively limit costimulation of naïve T-cells by mature dendritic cells and formation of a cytokine microenvironment that augments tolerized T-cells. REFERENCES

[0003] Agrawal, S., et al., Proc Natl Acad Sci USA 87(4):1401-5, (1990).

[0004] Akhtar, S., et al., Nucleic Acids Res 19(20):5551-9, (1991).

[0005] Anderson, C. M., et al., J Neurochem 73(2):867-73, (1999).

[0006] Anderson, K. P., et al., Antimicrob Agents Chemother 40(9):2004-11, (1996).

[0007] Bonham, M. A., et al., Nucleic Acids Res 23(7):1197-203, (1995).

[0008] Borriello, F., et al., J Immunol 155(12):5490-7, (1995).

[0009] Boudvillain, M., et al., Biochemistry 36(10):2925-31, (1997).

[0010] Cham...

Claims

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