Recombinant immunotoxin with T-cell epitope mutations that greatly reduce immunogenicity for treatment of mesothelin-expressing tumors

Molecular Cancer Therapeutics

Volumn 14, Issue 12, 2015, Pages 2789-2796

  Mazor, Ronit ^a   Zhang, Jingli ^a   Xiang, Laiman ^a   Addissie, Selamawit ^a   Awuah, Prince ^a   Beers, Richard ^a   Hassan, Raffit ^a   Pastan, Ira ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; EPITOPE; IMMUNOTOXIN; MESOTHELIN; BACTERIAL TOXIN; EXOTOXIN; GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORED PROTEIN; MONOCLONAL ANTIBODY; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; RECOMBINANT PROTEIN; SS1(DSFV)PE38; TOXA PROTEIN, PSEUDOMONAS AERUGINOSA; VIRULENCE FACTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CONTROLLED STUDY; CYTOKINE RELEASE; DRUG CYTOTOXICITY; DRUG POTENCY; GENE MUTATION; HUMAN; HUMAN CELL; IMMUNOGENICITY; MESOTHELIOMA CELL LINE; MOUSE; NONHUMAN; PRIORITY JOURNAL; T LYMPHOCYTE; ANIMAL; BIOSYNTHESIS; DRUG EFFECTS; DRUG SCREENING; GENETICS; IMMUNOGENETICS; IMMUNOLOGY; MESOTHELIOMA; MUTATION; TUMOR CELL LINE;

ADP RIBOSE TRANSFERASES; ANIMALS; ANTIBODIES, MONOCLONAL; BACTERIAL TOXINS; CELL LINE, TUMOR; EPITOPES, T-LYMPHOCYTE; EXOTOXINS; GPI-LINKED PROTEINS; HUMANS; IMMUNOGENETIC PHENOMENA; MESOTHELIOMA; MICE; MUTATION; RECOMBINANT PROTEINS; VIRULENCE FACTORS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84957631965     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-15-0532     Document Type: Article

References (30)

1. Kreitman RJ, Tallman MS, Robak T, Coutre S, Wilson WH, Stetler-Stevenson M, et al. Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia. J Clin Oncol 2012;30:1822-8.
2. Kreitman RJ, Wilson WH, White JD, Stetler-Stevenson M, Jaffe ES, Giardina S, et al. Phase I trial of recombinant immunotoxin anti-Tac (Fv)-PE38 (LMB-2) in patients with hematologic malignancies. JClin Oncol 2000;18:1622-36.
3. Hollevoet K, Mason-Osann E, Liu XF, Imhof-Jung S, Niederfellner G, Pastan I. In vitro and in vivo activity of the low-immunogenic antimesothelin immunotoxin RG7787 in pancreatic cancer. Mol Cancer Ther 2014;13:2040-9.
4. Alewine C, Xiang L, Yamori T, Niederfellner G, Bosslet K, Pastan I. Efficacy of RG7787, a next-generation mesothelin-targeted immunotoxin, against triple-negative breast and gastric cancers. Mol Cancer Ther 2014;13:2653-61.
5. Hassan R, Kreitman RJ, Pastan I, Willingham MC. Localization of mesothelin in epithelial ovarian cancer. Appl Immunohistochem Mol Morphol 2005;13:243-7.
6. Tang Z, Qian M, Ho M. The role of mesothelin in tumor progression and targeted therapy. Anticancer Agents Med Chem 2013;13:276-80.
7. Kreitman RJ, Hassan R, Fitzgerald DJ, Pastan I. Phase I trial of continuous infusion anti-mesothelin recombinant immunotoxin SS1P. Clin Cancer Res 2009;15:5274-9.
8. Hassan R, Bullock S, Premkumar A, Kreitman RJ, Kindler H, Willingham MC, et al. 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;13:5144-9.
9. Hassan R, Miller AC, Sharon E, Thomas A, Reynolds JC, Ling A, et al. Major cancer regressions in mesothelioma after treatment with an anti-mesothelin immunotoxin and immune suppression. Sci Transl Med 2013;5:208ra147.
10. Schellekens H. How to predict and prevent the immunogenicity of therapeutic proteins. Biotechnol Annu Rev 2008;14:191-202.
11. Malucchi S, Sala A, Gilli F, Bottero R, Di Sapio A, Capobianco M, et al. Neutralizing antibodies reduce the efficacy of betaIFN during treatment of multiple sclerosis. Neurology 2004;62:2031-7.
12. Baert F, Noman M, Vermeire S, Van Assche G, D'Haens G, Carbonez A, et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med 2003;348:601-8.
13. Onda M, Beers R, Xiang L, Nagata S, Wang QC, Pastan I. An immunotoxin with greatly reduced immunogenicity by identification and removal of B cell epitopes. Proc Natl Acad Sci U S A 2008;105:11311-6.
14. Yeung VP, Chang J, Miller J, Barnett C, Stickler M, 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;172:6658-65.
15. Mazor R, Eberle JA, Hu X, Vassall AN, Onda M, Beers R, et al. 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;111:8571-6.
16. Chowdhury PS, Viner JL, Beers R, Pastan I. Isolation of a high-affinity stable single-chain Fv specific for mesothelin from DNA-immunized mice by phage display and construction of a recombinant immunotoxin with antitumor activity. Proc Natl Acad Sci U S A 1998;95:669-74.
17. Pastan I, Beers R, Bera TK. Recombinant immunotoxins inthe treatment of cancer. Methods Mol Biol 2004;248:503-18.
18. Weldon JE, Xiang L, Chertov O, Margulies I, Kreitman RJ, Fitz Gerald DJ, et al. A protease-resistant immunotoxin against CD22 with greatly increased activity against CLL and diminished animal toxicity. Blood 2009;113:3792-800.
19. Ho M, Hassan R, Zhang J, Wang QC, Onda M, Bera T, et al. Humoral immune response to mesothelin in mesothelioma and ovarian cancer patients. Clin Cancer Res 2005;11:3814-20.
20. Zhang J, Qiu S, Zhang Y, Merino M, Fetsch P, Avital I, et al. Loss of mesothelin expression by mesothelioma cells grown in vitro determines sensitivity to anti-mesothelin immunotoxin SS1P. Anticancer Res 2012;32:5151-8.
21. Kalra N, Zhang J, Thomas A, Xi L, Cheung M, Talarchek J, et al. Mesothelioma patient derived tumor xenografts with defined BAP1 mutations that mimic the molecular characteristics of human malignant mesothelioma. BMC Cancer 2015;15:376.
22. Mazor R, Vassall AN, Eberle JA, Beers R, Weldon JE, Venzon DJ, et al. 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:E3597-603.
23. Musselli C, Livingston PO, Ragupathi G. Keyhole limpet hemocyanin conjugate vaccines against cancer: the Memorial Sloan Kettering experience. J Cancer Res Clin Oncol 2001;127:R20-6.
24. Tang Z, Feng M, Gao W, Phung Y, Chen W, Chaudhary A, et al. A human single-domain antibody elicits potent antitumor activity by targeting an epitope in mesothelin close to the cancer cell surface. Mol Cancer Ther 2013;12:416-26.
25. Pastan I, Hassan R. Discovery of mesothelin and exploiting it as a target for immunotherapy. Cancer Res 2014;74:2907-12.
26. Liu Z, Williams KP, Chang YH, Smith JA. Immunodominance: a single amino acid substitution within an antigenic site alters intramolecular selection of T-cell determinants. J Immunol 1993;151:1852-8.
27. Schlienger K, Craighead N, Lee KP, Levine BL, June CH. Efficient priming of protein antigen-specific human CD4 (+) T cells by monocyte-derived dendritic cells. Blood 2000;96:3490-8.
28. Jaber A, Baker M. Assessment of the immunogenicity of different interferon beta-1a formulations using ex vivo T-cell assays. J Pharm Biomed Anal 2007;43:1256-61.
29. Oseroff C, Sidney J, Kotturi MF, Kolla R, Alam R, Broide DH, et al. Molecular determinants of T cell epitope recognition to the common Timothy grass allergen. J Immunol 2010;185:943-55.
30. Zhang Y, Zhang Y, Gu W, Sun B. TH1/TH2 cell differentiation and molecular signals. Adv Exp Med Biol 2014;841:15-44.