Method for the generation of antigen-specific lymphocytes

Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing – Genetically modified micro-organism – cell – or virus

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

C424S093100, C424S093200, C435S069100, C435S069500, C435S069700

Reexamination Certificate

active

07939059

ABSTRACT:
The invention provides systems and methods for the generation of lymphocytes having a unique antigen specificity. In a preferred embodiment, the invention provides methods of virally infecting cells from bone marrow with one or more viral vectors that encode antigen-specific antibodies for the production of, for example B cells and T cells. In some embodiments, the viral vectors include an IRES or 2A element to promote separation of, for example, the α subunit and β subunit of a T cell receptor (TCR) or heavy and light chains of a B-cell antibody. The resulting lymphocytes, express the particular antibody that was introduced in the case of B cells and TCR in the case of T cells. The lymphocytes generated can be used for a variety of therapeutic purposes including the treatment of various cancers and the generation of a desired immune response to viruses and other pathogens. The resulting cells develop normally and respond to antigen both in vitro and in vivo. We also show that it is possible to modify the function of lymphocytes by using stem cells from different genetic backgrounds. Thus our system constitutes a powerful tool to generate desired lymphocyte populations both for research and therapy. Future applications of this technology may include treatments for infectious diseases, such as HIV/AIDS, cancer therapy, allergy, and autoimmune disease.

REFERENCES:
patent: 5830755 (1998-11-01), Nishimura et al.
patent: 7041438 (2006-05-01), Carpenter et al.
patent: 7531648 (2009-05-01), Kingsman et al.
patent: 2005/0238626 (2005-10-01), Yang et al.
Dietz et al. Cytother 2001;3:97-105.
Anderson, Hum Gene Ther 2002;13:1261-2.
Luo et al. Blood 2009;113:1422-31.
Barnden et at., “Defective TCR expression in transgenic mice constructed using cDNA-based α- and β-chain genes under the control of heterologous regulatory elements,”Immunology and Cell Biology, vol. 76, (1998), pp. 34-40.
Berg et al., “Expression of T-Cell Receptor Alpha-Chain Genes in Transgenic Mice,”Molecular and Cellular Biology, vol. 8, No. 12, Dec. 1998, pp. 5459-5469.
Berger et al. “Adoptive Transfer of Virus-Specific and Tumor-Specific T Cell Immunity,”Curr. Opin. Immunol. vol. 21, No. 2, 2009, pp. 224-232.
Blüthmann et al., T-cell-specific deletion of T-cell receptor transgenes allows functional rearrangement of endogenous α- and β-genes,Nature, vol. 334, Jul. 14, 1988, pp. 156-159.
Clay et al., “Efficient transfer of a tumor antigen-reactive TCR to human peripheral blood lymphocytes confers anti-tumor reactivity,”Journal of Immunologyvol. 163, No. 1 pp. 507-513 (Jul. 1, 1999).
Clay et al., “Potential use of T cell receptor genes to modify hematopoietic stem cells for the gene therapy of cancer,”Pathology Oncology Research, vol. 5, pp. 3-15 (1999).
Cooper et al., “Transfer of specificity for human immunodeficiency virus type 1 into primary human T lymphocytes by introduction of T-cell receptor genes,”Journal of Virology, vol. 74, pp. 8207-8212 (2000).
Déglon et al., “Self-Inactivating Lentiviral Vectors with Enhanced Transgene Expression as Potential Gene Transfer System in Parkinson's Disease,”Human Gene Therapy, vol. 11, Jan. 1, 2000, pp. 179-190.
Dembićet al., “Transfer of specificity by murine α and β T-cell receptor genes,”Nature, vol. 320, Mar. 20, 1986, pp. 232-238.
Dong et al,J. Experim. Med.200 (12), pp. 1547-1557 (2004).
Dudley et al., “Cancer Regression and Autoimmunity in Patients After Clonal Repopulation with Antitumor Lymphocytes,”Science, vol. 298, Oct. 25, 2002, pp. 850-854.
Dull et al., “A Third-Generation Lentivirus Vector with a Conditional Packaging Sysyem,”Journal of Virology, vol. 72, No. 11, Nov. 1998, pp. 8463-8471.
Finney et al., “Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product,”Journal of Immunology, vol. 161, pp. 2791-2797 (1998).
French Anderson,Hum Gene Ther13:1261-2 (2002).
Fujio et al., “Functional Reconstitution of Class II MHC-Restricted T Cell Immunity Mediated by Retroviral Transfer of the αβ TCR Complex,”J. Immunology, vol. 165, (2000), pp. 528-532.
Hozumi et al., “Establishment of efficient reaggregation culture system for gene tarnsfection into immature T cells by retroviral vectors,”Immunology Letters, vol. 71, No. 1, pp. 61-66 (Jan. 10, 2000).
Kessels et al., “Immunotherapy through TCR gene transfer,”Nature Immunology, vol. 2, No. 10, pp. 957-961 (Oct. 2001).
Kouskoff et al., “Cassette vectors directing expression of T cell receptor genes in transgenic mice,”Journal of Immunological Methods, vol. 180, (1995), pp. 273-280.
Lois et al., “Germline Transmission and Tissue-Specific Expression of Transgenes Delivered by Lentiviral Vectors,”Science, vol. 295, Feb. 1, 2002, pp. 868-872.
Mamalaki et al., “Positive and Negative Selection in Transgenic Mice Expressing a T-Cell Receptor Specific for Influenza Nucleoprotein and Endogenous Superantigen,”Developmental Immunology, vol. 3, (1993), pp. 159-174.
May et al. “Therapeutic haemoglobin synthesis in beta-0thalassaemic mice expressing lentivirus-encoded human beta-globulin,”Nature, vol. 406, pp. 82-86 (Jul. 6, 2000).
Mhashilkar et al., “Inhibition of human immunodeficiency virus type I replication in vitro in acutely and persistently infected human CD4+ mononuclear cells expressing murine and humanized anti-human immunodeficiency virus type 1 TAT single-chain variable fragment intrabodies,”Human Gene Therapy, vol. 10, pp. 1453-1467 (1999).
Moss, Paul A.H., “Redirecting T cell specificity by TCR gene transfer,”Nature Immunology, vol. 2, No. 10, Oct. 2001, pp. 900-901.
Orkin et al.,NIH Report, (Dec. 1995).
Pandya et al., “Lentivirus and foamy virus vectors: novel gene therapy tools,”Expert Opinion on Biological Therapy, vol. 1, pp. 17-40 (2001).
Patterson, “Statement of Amy Patterson, M.D.,” (Feb. 2000).
Pircher et al., “Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen,”Nature, vol. 342, Nov. 30. 1989, pp. 559-561.
Pogulis et al., “Retroviral-mediated expression of an MHC class I-restricted T cell receptor in the CD8 T cell compartment of bone marrow-reconstituted mice,”Human Gene Therapy, vol. 9, pp. 2285-2297 (1998).
Robbins et al., “Consistent, persistent, expression from modified retroviral vectors in murine hematopoietic stem cells,”Proceedings of the National Academy of Sciences of the United States of America, vol. 95, pp. 10182-10187 (Aug. 1998).
Robbins et al., “Viral vectors for gene therapy,”Pharmacol. Ther. vol. 80, No. 1, pp. 35-47 (1998).
Rosenburg, “Progress in human tumor immunology and immunotherapy,”Naturevol. 411, pp. 380-384 (2001).
Stanislawski et al., “Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer,”Nature Immunology, vol. 2, No. 10, pp. 926-970 (Oct. 10, 2001).
Uematsu et al., “In Transgenic Mice the Introduced Functional T Cell Receptor β Gene Prevents Expression of Endogenous β Genes,”Cell, vol. 52, Mar. 25, 1998, pp. 831-841.
Van Parijs et al., “Uncoupling IL-2 Signals that Regulate T Cell Proliferation, Survival, and Fas-Mediated Activation-Induced Cell Death,”Immunity, vol. 11, Sep. 1999, pp. 281-288.
Yang et al., “Generation of functional antigen-specific T cells in defined genetic backgrounds by retrovirus-mediated expression of TCR cDNAs in hematopoietic precursor cells,”Proceedings of the National Academy of Sciences of the United States of America, vol. 99, No. 9, pp. 6204-6209 (Apr. 30, 2002).
Yang et al.,PNAS, 102:12, pp. 4518-4523 (2005).
Yee et al.,PNAS, 99 (25) pp. 16168-16173 (2002).
Yee, C. et al., “Adoptive T cell therapy using antigen-speci

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Method for the generation of antigen-specific lymphocytes does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Method for the generation of antigen-specific lymphocytes, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for the generation of antigen-specific lymphocytes will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-2675779

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.