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E. E.S.E.E. W. 655. A USOO920.0036B2 (12) United States Patent (10) Patent No.: US 9.200,036 B2 Jaffee et al. (45) Date of Patent: Dec. 1, 2015 (54) MESOTHELIN VACCINES AND MODEL 5,795,872 A 8/1998 Ricigliano et al. SYSTEMS 5,830,463 A 11/1998 Duke et al. 5,951,976 A 9/1999 Segal 5,981,259 A 11/1999 Franzusoff (75) Inventors: Elizabeth Jaffee, Lutherville, MD (US); 6,033,674. A 3/2000 Jaffee et al. Ralph Hruban, Baltimore, MD (US) 6,051.237 A * 4/2000 Paterson .................... 424, 2001 6,083,502 A 7/2000 Pastan et al. (73) Assignee: The Johns Hopkins University, 6,153,430 A 1 1/2000 Pastan et al. Baltimore, MD (US) 6,171,777 B1 1/2001 Cook et al. s 6,224,868 B1 5/2001 Wong et al. (*) Notice: Subject to any disclaimer, the term of this 3. R $38, A.A. patent is extended or adjusted under 35 6,358,933 B1 3/2002 Aguilar Rubido et al. U.S.C. 154(b) by 0 days. 6,384,018 B1 5, 2002 Content et al. 6,448,086 B1 9, 2002 Khosravi et al. (21) Appl. No.: 13/293,357 6,475.9956,472.375 B1 110/2002 1/2002 RoyHoon et et al. al. 6,488,926 B1 12/2002 Khan et al. (22) Filed: Nov. 10, 2011 6,495,143 B2 12/2002 Lee et al. 6,500,432 B1 12/2002 Dalemans et al. (65) Prior Publication Data 6,770,445 B1* 8/2004 Scholler et al. ................ 435/71 7,375,183 B1* 5/2008 Pastan et al. .................. 530/350 US 2012/0076752 A1 Mar. 29, 2012 2002/00 19331 A1 2/2002 Cheever et al. 2002fOO34753 A1 3/2002 Yang et al. O O 2002/0051990 A1 5/2002 Ople et al. Related U.S. Application Data 2003/0211498 A1 11/2003 Morin et al. 2004/003784.0 A1 2/2004 Beier et al. (63) Continuation of application No. 12/049,763, filed on 2005/0249748 A1 11/2005 Sty Jr. et al. Mar. 17, 2008, now abandoned, which is a continuation-in-part of application No. 10/618,088, FOREIGN PATENT DOCUMENTS filed on Jul. 14, 2003, now abandoned. EP O 517925 A1 12, 1992 (60) Provisional application No. 60/475,783, filed on Jun. EP O 621285 A1 10, 1994 5, 2003, provisional application No. 60/414,931, filed JP 11-502710 A 3, 1999 on Sep. 30, 2002, provisional application No. W. 3. 8 s: A. E. applicationE. No.E.S.E.E. OU/39s soo, Illed on Jul 14, s WOW. 97.24132655. A1A 105T 1997 provisional application No. 60/918.267, filed on Mar. WO 97.25068 A2 7/1997 15, 2007. WO 98.53319 A2 11/1998 WO 99.28471 A2 6, 1999 (51) Int. Cl. (Continued) A6 IK38/00 (2006.01) C07K I4/00 (2006.01) OTHER PUBLICATIONS C07K 7/06 (2006.01) A6 IK39/00 (2006.01) Sensi et al., “Intralesional Selection of T Cell Clonotypes in the C07K 6/30 (2006.01) Immune Response to Melanoma Antigens Occurring During Vacci CI2N 15/85 (2006.01) nation.” Journal of Immunotherapy, May 1998, vol. 21, No. 3, pp. CO7K 4/47 (2006.01) 198-204. (52) U.S. Cl. Continued CPC ............... C07K 7/06 (2013.01); A61K 39/00II (Continued) (2013.01); C07K 16/30 (2013.01): CI2N 15/8509A61K2039/505 (2013.01); A0IK (2013.01); 2267/0331 A61K2039/522 (2013.01); Primary Examiner Michail- 0 Belyavskyi (2013.01); A61 K 2039/523 (2013.01); A61 K (74) Attorney, Agent, or Firm — Banner & Witcoff, Ltd. 2039/53 (2013.01); A61 K 2039/55522 (2013.01); A61 K 2039/6031 (2013.01); C07K 14/4748 (2013.01); C12N 27.10/16522 (57) ABSTRACT (2013.01); C12N 2740/13043 (2013.01) (58) Field of Classification Search Mesothelin can be used as an immunotherapeutic target. It None induces a cytolytic T cell response. Portions of mesothelin See application file for complete search history. which induce Such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for (56) References Cited raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti U.S. PATENT DOCUMENTS tumor therapeutics and prophylactics comprises a strongly 5,320,956 A 6/1994 Willingham et al. mesothelin-expressing, transformed peritoneal cell line. 5,498,698 A 3/1996 Yamaguchi et al. 5,723,318 A 3/1998 Yamaguchi et al. 5,763,183 A 6, 1998 Pesonen et al. 7 Claims, 24 Drawing Sheets US 9.200,036 B2 Page 2 (56) References Cited Yamaguchi, et al., “A Novel Cytokine Exhibiting Megakaryocyte Potentiating Activity From a Human Pancreatic Tumor Cell Line HPC-Y5.” 1994, The Journal of Biological Chemistry 269(2):805 FOREIGN PATENT DOCUMENTS 808. WO OO/20027 A2 4/2000 Angelakopoulos et al., “Safety and Shedding of an Attenuated Strain WO OO,36107 A2 6, 2000 of Listeria monocytogenes with a Deletion of actAplcB in Adult WO OOf 50900 A2 8, 2000 Volunteers: a Dose Escalation Study of Oral Inoculation'. Infection WO 00,73346 A1 12/2000 and Immunity, Jul. 2002, pp. 3592-3601, vol. 70, No. 7. WO 01, 18046 A2 3, 2001 Argani et al., “Mesothelin is Overexpressed in the Vast Majority of WO O1,5727O A2 8, 2001 Ductal Adenocarcinomas of the Pancreas: Identification of a New WO O1, 57 271 A2 8, 2001 Pancreatic Cancer Marker by Serial Analysis of Gene Expression WO O1/92581 A2 12/2001 (SAGE)”. Clinical Cancer Research, Dec. 2001, pp. 3862-3868, vol. WO O2/OO677 A1 1, 2002 7. WO O2/O55705 A2 T 2002 Arrington et al., “Plasmid Vectors Encoding Cholera Toxin or the WO O2/O68677 A2 9, 2002 WO O2/10.1075 A2 12/2002 Heat-Labile Enterotoxin from Escherichia coli are Strong Adjuvants WO 02/102235 A2 12/2002 fro DNA Vaccines”, Journal of Virology, May 2002, pp. 4536-4546, WO O3.014322 A2 2, 2003 vol. 76, No. 9. WO 03/042661 A2 5, 2003 Baltz, "Vaccines in the treatment of cancer'. Am J Health-Syst WO 03/050243 A2 6, 2003 Pharm, Nov. 15 1995, pp. 2574-2585, vol. 52. WO 2006/076678 A2 T 2006 Bera et al., “Mesothelin is Not Required for Normal Mouse Devel opment or Reproduction'. Molecular and Cellular Biology, Apr. OTHER PUBLICATIONS 2000, pp. 2902-2906, vol. 20, No. 8. Chang et al., “Flavivirus DNA Vaccines Current Status and Poten Berd et al., “Induction of Cell-Mediated Immunity to Autologous tial”. Ann New York Acad Sci., Dec. 2001, pp. 272-285, vol. 951. Melanoma Cells and Regression of Metastases. After Treatment With Chowdhury et al., “Analysis of cloned Fvs from a phage display a Melanoma Cell Vaccine Preceded by Cyclophosphamide.” Cancer library indicates that DNA immunization can mimic antibody Research, May 1986, vol. 46, pp. 2573-2577. response generated by cell immunizations', JIM. 1999, pp. 83-91, Hoon et al., “Suppressor Cell Activity in a Randomized Trial of vol. 231. Patients Receiving Active Specific Immunotherapy with Melanoma Chowdhury et al., “Generation of high titer antisera in rabbits by DNA immunization”, JIM. 2001, pp. 147-154, vol. 249. 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Darji et al., “Oral delivery of DNA vaccines using attenuated Salmo Argani, et al., “Discovery of New Markers of Cancer Through Serial nella typhimurium as carrier'. FEMS Immunology and Medical Analysis of Gene Expression: Prostate Stem Cell Antigen is Microbiology, 2000, pp. 341-349, vol. 27. Overexpressed in Pancreatic Adenocarcinoma.” Jun. 1, 2001, Cancer Glomski et al., “The Listeria monocytogenes hemolysin has an acidic Research 61:4320-4324. pH optimum to compartmentalize activity and prevent damage to Chang, et al., “Isolation and Characterization of a Monoclonal Anti infected host cells'. The Journal of Cell Biology, Mar. 18 2002, pp. body, K1, Reactive With Ovarian Cancers and Normal 1029-1038, vol. 156, No. 6. Mesothelium.” 1992, Int. J. Cancer 50 (3):373-381. Gunn et al., “Two Listeria monocytogenes Vaccine Vectors That Chang, et al., “Characterization of the Antigen (CAK1) Recognized Express Different Molecular Forms of Human Papilloma Virus-16 by Monoclonal Antibody K1 Present on Ovarian Cancers and Normal (HPV-16) E7 Induce Qualitatively Different T Cell Immunity That Mesothelium.” Jan. 1, 1992, Cancer Research 52: 181-186. Correlates with Their Ability to Induce Regression of Established Chang, et al., “Molecular Cloning of Mesothelin, A Differentiation Tumors Immortalized by HPV-16”. The Journal of Immunology, Antigen Present on Mesothelium, Mesotheliomas, and Ovarian Can 2001, pp. 6471-6479, vol. 167. cers,” Jan. 1996, PNAS USA93: 136-140. Hellström et al., “Tumor Immunology: An Overview”. Ann. New Hough, et al., "Large-Scale Serial Analysis of Gene Expression York Acad.
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