Dual B- and T-cell de-immunization of recombinant immunotoxin targeting mesothelin with high cytotoxic activity

Oncotarget

Volumn 7, Issue 21, 2016, Pages 29916-29926

  Mazor, Ronit ^a   Onda, Masanori ^a   Park, Dong ^a,b   Addissie, Selamawit ^a   Xiang, Laiman ^a   Zhang, Jingli ^a   Hassan, Raffit ^a   Pastan, Ira ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b Microbial Toxin Research Institute   (South Korea)

Author keywords

Epitope; Immunogenicity; Mesothelioma; Pancreatic cancer; Rational design

Indexed keywords

AMINO ACID; EPITOPE; IMMUNOTOXIN; IMMUNOTOXIN LMB T14; IMMUNOTOXIN LMB T20; IMMUNOTOXIN LO10R; IMMUNOTOXIN SS1P; MESOTHELIN; UNCLASSIFIED DRUG; BACTERIAL TOXIN; EXOTOXIN; GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORED PROTEIN; HYBRID PROTEIN; MONOCLONAL ANTIBODY;

ADAPTIVE IMMUNITY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; B LYMPHOCYTE; CANCER CELL LINE; CANCER IMMUNIZATION; CANCER REGRESSION; CONTROLLED STUDY; DRUG ANTIGENICITY; DRUG BINDING SITE; DRUG CYTOTOXICITY; DRUG DOSE COMPARISON; DRUG STABILITY; DRUG STRUCTURE; DRUG TARGETING; DRUG TOLERABILITY; FEMALE; HUMAN; HUMAN CELL; IMMUNOCYTOTOXICITY; MESOTHELIOMA; MOUSE; MULTIPLE CYCLE TREATMENT; NONHUMAN; POINT MUTATION; SINGLE DRUG DOSE; STRUCTURE ANALYSIS; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TUMOR XENOGRAFT; ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG SCREENING; GENETICS; HELPER CELL; IMMUNOGLOBULIN VARIABLE REGION; IMMUNOLOGY; IMMUNOTHERAPY; LUNG TUMOR; MOLECULARLY TARGETED THERAPY; MUTATION; NUDE MOUSE; PROCEDURES; PROTEIN ENGINEERING; TUMOR CELL LINE;

ADAPTIVE IMMUNITY; ANIMALS; ANTIBODIES, MONOCLONAL; BACTERIAL TOXINS; CELL LINE, TUMOR; EPITOPES, B-LYMPHOCYTE; EPITOPES, T-LYMPHOCYTE; EXOTOXINS; FEMALE; GPI-LINKED PROTEINS; HUMANS; IMMUNOGLOBULIN VARIABLE REGION; IMMUNOTHERAPY; IMMUNOTOXINS; LUNG NEOPLASMS; MESOTHELIOMA; MICE; MICE, NUDE; MOLECULAR TARGETED THERAPY; MUTATION; PROTEIN ENGINEERING; RECOMBINANT FUSION PROTEINS; T-LYMPHOCYTES, HELPER-INDUCER; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84971517469     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.9171     Document Type: Article

References (32)

1. Hassan R, Kreitman RJ, Pastan I and Willingham MC. Localization of mesothelin in epithelial ovarian cancer. Appl Immunohistochem Mol Morphol. 2005;13:243-247.
2. Tang Z, Qian M and Ho M. The role of mesothelin in tumor progression and targeted therapy. Anticancer Agents Med Chem. 2013; 13:276-280.
3. Hollevoet K, Mason-Osann E, Liu XF, Imhof-Jung S, Niederfellner G and Pastan I. In vitro and in vivo activity of the low-immunogenic antimesothelin immunotoxin RG7787 in pancreatic cancer. Mol Cancer Ther. 2014;13:2040-2049.
4. Alewine C, Xiang L, Yamori T, Niederfellner G, Bosslet K and Pastan I. Efficacy of RG7787, a next-generation mesothelin-targeted immunotoxin, against triple-negative breast and gastric cancers. Mol Cancer Ther. 2014; 13:2653-2661.
5. Hassan R, Bullock S, Premkumar A, Kreitman RJ, Kindler H, Willingham MC and Pastan I. Phase I study of SS1P, a recombinant anti-mesothelin immunotoxin given as a bolus I.V. infusion to patients with mesothelin-expressing mesothelioma, ovarian, and pancreatic cancers. Clin Cancer Res. 2007; 13:5144-5149.
6. Hassan R, Miller AC, Sharon E, Thomas A, Reynolds JC, Ling A, Kreitman RJ, Miettinen MM, Steinberg SM, Fowler DH and Pastan I. Major cancer regressions in mesothelioma after treatment with an anti-mesothelin immunotoxin and immune suppression. Sci Transl Med. 2013; 5:208ra147.
7. Krishna M and Nadler SG. Immunogenicity to biotherapeutics-the role of anti-drug immune complexes. Front Immunol. 2016; 7:21.
8. Mazor R, Onda M and Pastan I. Immunogenicity of therapeutic recombinant immunotoxins. Immunol Rev. 2016; 270:152-164.
9. Collen D, Bernaerts R, Declerck P, De Cock F, Demarsin E, Jenne S, Laroche Y, Lijnen HR, Silence K and Verstreken M. Recombinant staphylokinase variants with altered immunoreactivity. I: Construction and characterization. Circulation. 1996; 94:197-206.
10. Onda M, Beers R, Xiang L, Lee B, Weldon JE, Kreitman RJ and Pastan I. Recombinant immunotoxin against B-cell malignancies with no immunogenicity in mice by removal of B-cell epitopes. Proc Natl Acad Sci U S A. 2011; 108:5742-5747.
11. Liu W, Onda M, Lee B, Kreitman RJ, Hassan R, Xiang L and Pastan I. Recombinant immunotoxin engineered for low immunogenicity and antigenicity by identifying and silencing human B-cell epitopes. Proc Natl Acad Sci U S A. 2012; 109:11782-11787.
12. Yeung VP, Chang J, Miller J, Barnett C, Stickler M and Harding FA. Elimination of an immunodominant CD4+ T cell epitope in human IFN-beta does not result in an in vivo response directed at the subdominant epitope. J Immunol. 2004; 172:6658-6665.
13. Mazor R, Crown D, Addissie S, Jang Y, Kaplan G and Pastan I. Elimination of murine and human T-cell epitopes in recombinant immunotoxin eliminates neutralizing and anti-drug antibodies in vivo. Cell Mol Immunol. 2015; doi: 10.1038/cmi.2015.91.
14. Mazor R, Eberle JA, Hu X, Vassall AN, Onda M, Beers R, Lee EC, Kreitman RJ, Lee B, Baker D, King C, Hassan R, Benhar I and Pastan I. Recombinant immunotoxin for cancer treatment with low immunogenicity by identification and silencing of human T-cell epitopes. Proc Natl Acad Sci U S A. 2014; 111:8571-8576.
15. Mazor R, Zhang J, Xiang L, Addissie S, Awuah P, Beers R, Hassan R and Pastan I. Recombinant immunotoxin with T-cell epitope mutations that greatly reduce immunogenicity for treatment of mesothelin-expressing tumors. Mol Cancer Ther. 2015; 14:2789-2796.
16. Weldon JE, Xiang L, Chertov O, Margulies I, Kreitman RJ, FitzGerald DJ and Pastan I. A protease-resistant immunotoxin against CD22 with greatly increased activity against CLL and diminished animal toxicity. Blood. 2009; 113:3792-3800.
17. Pastan I and Hassan R. Discovery of mesothelin and exploiting it as a target for immunotherapy. Cancer Res. 2014; 74:2907-2912.
18. Zhang J, Qiu S, Zhang Y, Merino M, Fetsch P, Avital I, Filie A, Pastan I and Hassan R. Loss of mesothelin expression by mesothelioma cells grown in vitro determines sensitivity to anti-mesothelin immunotoxin SS1P. Anticancer Res. 2012; 32:5151-5158.
19. Hassan R, Williams-Gould J, Watson T, Pai-Scherf L and Pastan I. Pretreatment with rituximab does not inhibit the human immune response against the immunogenic protein LMB-1. Clin Cancer Res. 2004; 10(1 Pt 1):16-18.
20. Ansari HR and Raghava GP. Identification of conformational B-cell Epitopes in an antigen from its primary sequence. Immunome Res. 2010; 6:6.
21. Bogan AA and Thorn KS. Anatomy of hot spots in protein interfaces. J Mol Biol. 1998; 280:1-9.
22. Kaliyaperumal A, Michaels MA and Datta SK. Naturally processed chromatin peptides reveal a major autoepitope that primes pathogenic T and B cells of lupus. J Immunol. 2002; 168:2530-2537.
23. Ratto-Kim S, de Souza MS, Currier JR, Karasavvas N, Sidney J, Rolland M, Valencia-Micolta A, Madnote S, Sette A, Nitayaphan S, Pitisuttuthum P, Kaewkungwal J, Rerks-Ngarm S, O'Connell R, Michael N, Robb ML, et al. Identification of immunodominant CD4-restricted epitopes co-located with antibody binding sites in individuals vaccinated with ALVAC-HIV and AIDSVAX B/E. PloS One. 2015; 10:e0115582.
24. Barnett BC, Burt DS, Graham CM, Warren AP, Skehel JJ and Thomas DB. I-Ad restricted T cell recognition of influenza hemagglutinin. Synthetic peptides identify multiple epitopes corresponding to antibody-binding regions of the HA1 subunit. J Immunol. 1989; 143:2663-2669.
25. Allen PM, Matsueda GR, Evans RJ, Dunbar JB, Jr., Marshall GR and Unanue ER. Identification of the T-cell and Ia contact residues of a T-cell antigenic epitope. Nature. 1987; 327:713-715.
26. Johansen BH, Vartdal F, Eriksen JA, Thorsby E and Sollid LM. Identification of a putative motif for binding of peptides to HLA-DQ2. Int Immunol. 1996; 8:177-182.
27. Vita R, Overton JA, Greenbaum JA, Ponomarenko J, Clark JD, Cantrell JR, Wheeler DK, Gabbard JL, Hix D, Sette A and Peters B. The immune epitope database (IEDB) 3.0. Nucleic Acids Res. 2015; 43:D405-412.
28. Chowdhury PS, Chang K and Pastan I. Isolation of antimesothelin antibodies from a phage display library. MolImmunol. 1997; 34:9-20.
29. Pastan I, Beers R and Bera TK. Recombinant immunotoxins in the treatment of cancer. Methods Mol Biol. 2004; 248:503-518.
30. Oseroff C, Sidney J, Kotturi MF, Kolla R, Alam R, Broide DH, Wasserman SI, Weiskopf D, McKinney DM, Chung JL, Petersen A, Grey H, Peters B and Sette A. Molecular determinants of T cell epitope recognition to the common Timothy grass allergen. J Immunol. 2010; 185:943-955.
31. Mazor R, Vassall AN, Eberle JA, Beers R, Weldon JE, Venzon DJ, Tsang KY, Benhar I and Pastan I. Identification and elimination of an immunodominant T-cell epitope in recombinant immunotoxins based on Pseudomonas exotoxin A. Proc Natl Acad Sci U S A. 2012; 109:E3597-3603.
32. Ho M, Hassan R, Zhang J, Wang QC, Onda M, Bera T and Pastan I. Humoral immune response to mesothelin in mesothelioma and ovarian cancer patients. Clin Cancer Res. 2005; 11:3814-3820.