Immunotherapy against several tumors including neuronal and brain tumors

12234,298

17/238787

April 23, 2021

The present invention relates to peptides, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention relates to 30 peptide sequences and their variants derived from HLA class I and class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.

IMMATICS BIOTECHNOLOGIES GMBH (Tuebingen, DE)

Immatics Biotechnologies GmbH (Tübingen, DE)

1. An isolated peptide consisting of the amino acid sequence ALAVLSNYDA (SEQ ID NO: 9) in the form of a pharmaceutically acceptable salt, wherein said peptide is produced by solid phase peptide synthesis or produced by a yeast cell or bacterial cell expression system.

2. The peptide of claim 1 , wherein the pharmaceutically acceptable salt is chloride salt.

3. The peptide of claim 1 , wherein the pharmaceutically acceptable salt is acetate salt.

4. A composition comprising the peptide of claim 1 and a pharmaceutically acceptable carrier.

5. The composition of claim 4 , wherein the peptide is in the form of a chloride salt.

6. The composition of claim 4 , wherein the peptide is in the form of an acetate salt.

7. The composition of claim 4 , further comprising an adjuvant selected from the group consisting of anti-CD40 antibody, imiquimod, resiquimod, GM-CSF, cyclophosphamide, sunitinib, bevacizumab, interferon-alpha, interferon-beta, CpG oligonucleotides, poly-(I:C), RNA, sildenafil, particulate formulations with poly (lactide co-glycolide) (PLG), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23.

8. The composition of claim 7 , wherein the adjuvant is IL-2.

9. The composition of claim 7 , wherein the adjuvant is IL-7.

10. The composition of claim 7 , wherein the adjuvant is IL-12.

11. The composition of claim 7 , wherein the adjuvant is IL-15.

12. The composition of claim 7 , wherein the adjuvant is IL-21.

13. A composition comprising the peptide of claim 1 , wherein the composition is a pharmaceutical composition and comprises water and a buffer.

14. The composition of claim 7 , wherein the adjuvant is IL-1.

15. The composition of claim 7 , wherein the adjuvant is IL-23.

16. The composition of claim 7 , wherein the adjuvant is IL-4.

17. The composition of claim 7 , wherein the adjuvant is IL-13.

6589642 July 2003 Miller
6992176 January 2006 Reiter
7919467 April 2011 Ramakrishna
8008431 August 2011 Weinschenk et al.
8119139 February 2012 Weinschenk
8242239 August 2012 Weinschenk
8318677 November 2012 Weinschenk
8653035 February 2014 Weinschenk
8669063 March 2014 Weinschenk
8747855 June 2014 Reiter et al.
8895514 November 2014 Weinschenk et al.
8961985 February 2015 Weinschenk
9283267 March 2016 Lewandrowski
9289478 March 2016 Lewandrowski
9901629 February 2018 Sonntag et al.
9993540 June 2018 Weinschenk et al.
10035838 July 2018 Sonntag et al.
10046037 August 2018 Weinschenk et al.
10047123 August 2018 Weinschenk et al.
10047124 August 2018 Weinschenk et al.
10100085 October 2018 Weinschenk et al.
10227381 March 2019 Weinschenk et al.
10364281 July 2019 Sonntag et al.
10385110 August 2019 Sonntag et al.
10385111 August 2019 Sonntag et al.
10435454 October 2019 Sonntag et al.
10464991 November 2019 Sonntag et al.
10640547 May 2020 Sonntag et al.
10906936 February 2021 Weinschenk et al.
10919931 February 2021 Weinschenk et al.
10941181 March 2021 Weinschenk et al.
11136352 October 2021 Weinschenk et al.
11208434 December 2021 Weinschenk et al.
2002/0090672 July 2002 Rosen
2003/0175733 September 2003 Kirst
2005/0261166 November 2005 Wang
2006/0241166 October 2006 Magda
2008/0207497 August 2008 Ramakrishna
2010/0021441 January 2010 Weinschenk et al.
2010/0029573 February 2010 Weinschenk et al.
2010/0158929 June 2010 Lewandrowski et al.
2010/0158931 June 2010 Weinschenk et al.
2011/0002963 January 2011 Weinschenk et al.
2011/0142919 June 2011 Ramakrishna
2012/0107337 May 2012 Lewandrowski
2012/0141517 June 2012 Weinschenk
2013/0004456 January 2013 Weinschenk et al.
2013/0045191 February 2013 Weinschenk
2013/0309193 November 2013 Weinschenk
2014/0234347 August 2014 Weinschenk
2015/0125478 May 2015 Weinschenk et al.
2016/0355550 December 2016 Weinschenk et al.
2016/0376312 December 2016 Weinschenk et al.
2016/0376313 December 2016 Weinschenk et al.
2016/0376314 December 2016 Weinschenk et al.
2016/0376315 December 2016 Weinschenk et al.
2016/0376316 December 2016 Weinschenk et al.
2016/0376317 December 2016 Weinschenk et al.
2017/0305991 October 2017 Sonntag et al.
2017/0326216 November 2017 Sonntag et al.
2017/0326217 November 2017 Weinschenk et al.
2018/0193439 July 2018 Sonntag et al.
2019/0010190 January 2019 Weinschenk et al.
2019/0040112 February 2019 Sonntag et al.
2019/0040113 February 2019 Sonntag et al.
2019/0040114 February 2019 Sonntag et al.
2019/0040115 February 2019 Sonntag et al.
2019/0062401 February 2019 Sonntag et al.
2019/0201443 July 2019 Joglekar et al.
2019/0389930 December 2019 Sonntag et al.
2021/0238227 August 2021 Weinschenk et al.
2021/0253637 August 2021 Weinschenk et al.
2021/0261614 August 2021 Weinschenk et al.
2021/0347822 November 2021 Weinschenk et al.
109069587 December 2018
0570188 November 1993
0570188 November 1993
1835027 September 2007
2111867 October 2009
2111867 October 2009
101184869 September 2012
9831797 July 1998
9831797 July 1998
200155368 August 2001
200155368 August 2001
2002020036 March 2002
2002020036 March 2002
2002046767 June 2002
2002046767 June 2002
2002074237 September 2002
2002074237 September 2002
2003045998 June 2003
2003045998 June 2003
2004015390 February 2004
2004015390 February 2004
2005116051 December 2005
2005116051 December 2005
2007072505 June 2007
2007072505 June 2007
2007150077 December 2007
2007150077 December 2007
2008109757 September 2008
2008109757 September 2008
2010037514 April 2010
2010037514 April 2010
2017182395 October 2017

Berge et al. (J. Pharm. Sci. Jan. 1977; 66 (1): 1-19). cited by examiner
Paulekuhn et al. (J. Med. Chem. Dec. 27, 2007; 50 (26): 6665-72). cited by examiner
Nakagawa et al. (Biophys J. Apr. 1, 2007; 92 (7): 2570-82). cited by examiner
He et al. (Life Sci. 1999; 65 (4): 355-68). cited by examiner
Sikora et al. (Pharmaceuticals (Basel). Dec. 2020; 13 (12): 442; pp. 1-29). cited by examiner
Bilich et al. (Blood. Feb. 7, 2019; 133 (6): 550-565). cited by examiner
Stevens et al. (Eur. J. Immunol. Apr. 1998; 28 (4): 1272-9). cited by examiner
Hervé et al. (Mol. Immunol. Feb. 1997; 34 (2): 157-63). cited by examiner
Berge, Stephen M., et al., Pharmaceutical salts, Journal of pharmaceutical, 1977, 66, 1 1977. cited by applicant
Paulekuhn, G. Steffen, Jennifer B. Dressman, and Christoph Saal. “Trends in active pharmaceutical ingredient salt selection based on analysis of the orange book database.” Journal of medicinal chemistry 50, No. 26 (2007) 2007. cited by applicant
Nakagawa, Yohko, Hiroto Kikuchi, and Hidemi Takahashi. “Molecular analysis of TCR and peptide/MHC interaction using P18-I10-derived peptides with a single D-amino acid substitution.” Biophysical journal 92, No. 7 (2007). 2007. cited by applicant
Udaka, Keiko, et al., An automated prediction of MHC class I-binding peptides based on positional scanning with peptide libraries., Immunogenetics , 2000, 51 2000. cited by applicant
Ljunggren, Hans-Gustaf, Nico J. Stam, Claes Öhlén, Jacques J. Neefjes, Petter Höglund, Marie-Thérèse Heemels, Judy Bastin et al. “Empty MHC class I molecules come out in the cold.” Nature 346, No. 6283 (1990). 1990. cited by applicant
Bilich, Tatjana, et al., The HLA ligandome landscape of chronic myeloid leukemia delineates novel T-cell epitopes for immunotherapy., Blood, The Journal of the, 2019, 133, 6 2019. cited by applicant
He, Xian-Hui, Pang-Chui Shaw, and Siu-Cheung Tam. “Reducing the immunogenicity and improving the in vivo activity of trichosanthin by site-directed pegylation.” Life sciences 65, No. 4 (1999). 1999. cited by applicant
Hervé, Mireille, Bernard Maillére, Gilles Mourier, Catherine Texier, Sandrine Leroy, and Andre Ménez. “On the immunogenic properties of retro-inverso peptides. Total retro-inversion of T-cell epitopes causes a loss of binding to MHC II molecules.” Molecular immunology 34, No. 2 (1997). 1997. cited by applicant
Stevens, James, et al., Peptide length preferences for rat and mouse MHC class I molecules using random peptide libraries., European journal of immun, 1998, 28, 4 1998. cited by applicant
Uniprot Accession No. A2T6A1; sequence version 1 (Feb. 6, 2007). cited by applicant
Uniprot Accession No. A1YGC8; sequence version 1 (Feb. 6, 2007). cited by applicant
Extended European Search Report, EP 08 01 7921, Dec. 14, 2009. cited by applicant
Gunther et al., “Glioblastoma-derived stem cell-enriched cultures from distinct subgroups according to molecular and phenotypic criteria,” Oncogen (2008) 27, 00. 2897-2909 (XP-002557755). cited by applicant
Suzuki et al., “Genetic analysis of human glioblastomas using a genomic microarray system,” Brain Tumore Pathol (2004) 21, pp. 27-34 (XP-002557756). cited by applicant
Shibahara et al., “Podoplanin is expressed in subsets of tumors of the central nervous system,” Virchows Arch (2006) 448, pp. 493-499 (XP-002557757). cited by applicant
International Journal of Cancer, Journal of International DU Cancer, May 18, 1998, vol. 77: 04, pp. 451-458. cited by applicant
Gary et al., “cDNS Cloning, chromosomal localization, and expression analysis of human BEHAB/brevican, a brain specification proteoglycan regulated during cortical development and in glioma,” Gene, Elsevier, Amsterdam, NL, vol. 256: 1-2, Oct. 3, 2000, pp. 139-147 (XP-004238299). cited by applicant
International Preliminary Report on Patentability dated Apr. 5, 2011 from PCT/EP2009/006980 and Written Opinion, dated Apr. 1, 2011. cited by applicant
International Search Report dated Mar. 30, 2010 from PCT/EP2009/006980. cited by applicant
International Search Report dated Sep. 26, 2008 from PCT/EP2009/006980. cited by applicant
Meydan et al. (BMC Bioinformatics. 2013; 14 (Suppl. 2): S13; pp. 1-12). cited by applicant
Neefjes et al. (Nature Reviews Immunology. Dec. 2011; 11, 823-836). cited by applicant
Walter et al. (J. Immunol. Nov. 2003. 15; 171 (10): 4974-78). cited by applicant
Chen et al. (Arthritis Rheumatol. Feb. 2014; 66 (2): 284-94). cited by applicant
Li et al. (Front. Immunol. Nov. 2013. 22; 4: 383; pp. 1-8). cited by applicant
Obermann et al. (Immunology Sep. 2007; 122 (1): 90-97). cited by applicant
Mizukami et al. (Cancer Sci. Jul. 2008. 99(7): 1448-54). cited by applicant
Suda et al. (Cancer Sci. Nov. 2007; 98(1): 1803-08). cited by applicant
Delamarre et al. (Science. Mar. 11, 2005; 307 (5715): 1630-34). cited by applicant
Urban et al. (Proc. Natl. Acad. Sci. USA. Feb. 15, 1994; 91(4): 1534-38). cited by applicant
Chang et al. (Proc. Natl. Acad. Sci. USA. Nov. 22, 2005; 102(47): 17107-12). cited by applicant
Pascolo et al. (J. Exp. Med. Jun. 16, 1997; 185 (12); 2043-51). cited by applicant
Prakash, et al., “Gastrointestinal Stromal Tumors in Children and Young Adults A Clinicopathologic, Molecular, and Genomic Study of 15 Cases and Review of the Literature,” J. Pediatr Hematol Oncol, 27(4): 179-187 (Apr. 2005). cited by applicant

edspgr.12234298