Antigen-specific T cell receptors and T cell epitopes
| Title: | Antigen-specific T cell receptors and T cell epitopes |
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| Patent Number: | 9,586,997 |
| Publication Date: | March 07, 2017 |
| Appl. No: | 13/823079 |
| Application Filed: | September 19, 2011 |
| Abstract: | The present invention relates to efficient methods for providing antigen-specific lymphoid cells. These lymphoid cells may be used to provide antigen specific T cell receptors having a defined MHC restriction and to identify immunologically relevant T cell epitopes. Furthermore, the present invention relates to antigen-specific T cell receptors and T cell epitopes and their use in immunotherapy. |
| Inventors: | Sahin, Ugur (Mainz, DE); Tureci, Ozlem (Mainz, DE); Simon, Petra (Mainz, DE); Omokoko, Tana (Mainz, DE) |
| Assignees: | BioNtech Cell & Gene Therapies GmbH (Mainz, DE), Translationale Onkologie an der Universitatsmedizin der Johannes Gutenberg-Universitat Mainz gemeinnutzige GmbH (Mainz, DE) |
| Claim: | 1. An antigen-specific lymphoid cell produced by transferring into a lymphoid cell (i) a nucleic acid encoding a T cell receptor α-chain comprising the T cell receptor α-chain sequence of SEQ ID NO: 44 and a nucleic acid encoding a T cell receptor β-chain comprising the T cell receptor β-chain sequence of SEQ ID NO: 45 or (ii) a nucleic acid encoding a T cell receptor comprising the T cell receptor α-chain sequence of SEQ ID NO: 44 and the T cell receptor β-chain sequence of SEQ ID NO: 45. |
| Claim: | 2. A pharmaceutical composition comprising the antigen-specific lymphoid cell of claim 1 . |
| Claim: | 3. An antigen-specific lymphoid cell produced by transferring into a lymphoid cell (i) a nucleic acid encoding a T cell receptor α-chain comprising all three of the CDR sequences of the T cell receptor α-chain sequence of SEQ ID NO: 44 and a nucleic acid encoding a T cell receptor β-chain comprising all three of the CDR sequences of the T cell receptor β-chain sequence of SEQ ID NO: 45 or (ii) a nucleic acid encoding a T cell receptor comprising all three of the CDR sequences of the T cell receptor α-chain sequence of SEQ ID NO: 44 and all three of the CDR sequences the T cell receptor β-chain sequence of SEQ ID NO: 45. |
| Claim: | 4. A pharmaceutical composition comprising the antigen-specific lymphoid cell of claim 3 . |
| Claim: | 5. The antigen-specific lymphoid cell of claim 1 , wherein the nucleic acid is RNA. |
| Claim: | 6. The antigen-specific lymphoid cell of claim 5 , wherein the RNA is in vitro transcribed RNA (IVT RNA). |
| Claim: | 7. The antigen-specific lymphoid cell of claim 1 , wherein the lymphoid cell is selected from the group consisting of a lymphocyte, lymphoblast and plasma cell. |
| Claim: | 8. The antigen-specific lymphoid cell of claim 1 , wherein the lymphoid cell is a T cell lacking endogenous expression of a T cell receptor. |
| Claim: | 9. The antigen-specific lymphoid cell of claim 3 , wherein the nucleic acid is RNA. |
| Claim: | 10. The antigen-specific lymphoid cell of claim 9 , wherein the RNA is in vitro transcribed RNA (IVT RNA). |
| Claim: | 11. The antigen-specific lymphoid cell of claim 3 , wherein the lymphoid cell is selected from the group consisting of a lymphocyte, lymphoblast and plasma cell. |
| Claim: | 12. The antigen-specific lymphoid cell of claim 3 , wherein the lymphoid cell is a T cell lacking endogenous expression of a T cell receptor. |
| Patent References Cited: | 7259247 August 2007 Kroczek 2005/0261489 November 2005 Kroczek 2009/0042798 February 2009 Wang et al. 2009/0208538 August 2009 Darnell 2008-263950 November 2008 2008263950 November 2008 99/13095 March 1999 WO 0123560 April 2001 WO 0155393 August 2001 01/90197 November 2001 2005/016962 February 2005 2005/026205 March 2005 2006/026002 March 2006 2010/008782 January 2010 2010/105298 September 2010 |
| Other References: | Reiser et al. (Acta Crystallogr Sect F Struct Biol Cryst Commun. Nov. 1, 2009;65(Pt 11):1157-61). cited by examiner Comments of Olivier Kassel posted Nov. 6, 2012 on ResearchGate in response to the question: “Can anybody suggest a method / vector to express peptides (25 mer) in animal cells without using fusion protein or large tags?,” one page. cited by examiner Machine language translation of JP2008263950, pp. 1-46. cited by examiner Schumacher (Nat Rev Immunol. Jul. 2002;2(7):512-9). cited by examiner Uckert et al. (Cancer Immunol Immunother (2009) 58:809-822). cited by examiner Boulter et al. (Clinical and Experimental Immunology, 142: 454-460). cited by examiner Janeway et al., Immunobiology, 5th Ed., Garland Science, pp. 106-108, 117-118 and 260-263, (2001). cited by examiner Goyarts et al., Mol Immunol. Jul. 1998;35(10):593-607. cited by examiner Kessels et al., Proc Natl Acad Sci U S A. Dec. 19, 2000;97(26):14578-83. cited by examiner Stanislawski et al., “Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer”, Nature Immunology, 2001, 2(10), 962-970. cited by applicant Zhao et al., “Primary human lymphocytes transduced with NY-ESO-1 antigen-specific TCR genes recognize and kill diverse human tunior cell lines”, Journal of Immunology, 2005, 174(7), 4415-4423. cited by applicant Morris et al., “Prospects for immunotherapy of malignant disease”, Clinical and Experimental Immunology, 2003, 131(1), 1-7. cited by applicant Kessels et al., “Immunotherapy through TCR gene transfer”, Nature Immunology, 2001, 2(10), 957-961. cited by applicant Mandic M. et al., One NY-ESO-1 derived epitope that promiscuously binds to multiple HLA-DR and HLA-DP4 molecules and stimulates autologous CD4+ T cells from patients with NY-ESO-1-expressing melanoma, J. Immunol, 174 (3), p. 1751-1759 (2005). cited by applicant Busson et al., “Prediction of CD4+ T cell epitopes restricted to Hla-DP4 molecules,” Journal of Immunological Methods, vol. 317, Issues 1-2, Dec. 20, 2006, pp. 144-151. cited by applicant |
| Primary Examiner: | Skelding, Zachary |
| Attorney, Agent or Firm: | McDonnell Boehnen Hulbert & Berghoff LLP |
| Accession Number: | edspgr.09586997 |
| Database: | USPTO Patent Grants |
| Language: | English |
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