Immunotherapy

COVA4231, a potent CD3/CD33 bispecific FynomAb with IgG-like pharmacokinetics for the treatment of acute myeloid leukemia

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1
Fig. 2

References

  1. 1.

    Godwin CD, Gale RP, Walter RB. Gemtuzumab ozogamicin in acute myeloid leukemia. Leukemia. 2017;31:1855–68.

    CAS  Article  Google Scholar 

  2. 2.

    Wilke AC, Gökbuget N. Clinical applications and safety evaluation of the new CD19 specific T-cell engager antibody construct blinatumomab. Expert Opin Drug Saf. 2017;16:1191–202.

    CAS  Article  Google Scholar 

  3. 3.

    Walter RB. Investigational CD33-targeted therapeutics for acute myeloid leukemia. Expert Opin Investig Drugs. 2018;27:339–48.

    CAS  Article  Google Scholar 

  4. 4.

    Zhu M, Wu B, Brandl C, Johnson J, Wolf A, Chow A, et al. Blinatumomab, a Bispecific T-cell Engager (BiTE(®)) for CD-19 targeted cancer immunotherapy: clinical pharmacology and its implications. Clin Pharmacokinet. 2016;55:1271–88.

    CAS  Article  Google Scholar 

  5. 5.

    Grabulovski D, Kaspar M, Neri D. A novel, non-immunogenic Fyn SH3-derived binding protein with tumor vascular targeting properties. J Biol Chem. 2007;282:3196–204.

    CAS  Article  Google Scholar 

  6. 6.

    Schlatter D, Brack S, Banner DW, Batey S, Benz J, Bertschinger J, et al. Generation, characterization and structural data of chymase binding proteins based on the human Fyn kinase SH3 domain. MAbs. 2012;4:497–508.

    Article  Google Scholar 

  7. 7.

    Brack S, Attinger-Toller I, Schade B, Mourlane F, Klupsch K, Woods R, et al. A bispecific HER2-targeting FynomAb with superior antitumor activity and novel mode of action. Mol Cancer Ther. 2014;13:2030–9.

    CAS  Article  Google Scholar 

  8. 8.

    Pessano S, Oettgen H, Bhan AK, Terhorst C. The T3/T cell receptor complex: antigenic distinction between the two 20-kd T3 (T3-delta and T3-epsilon) subunits. EMBO J. 1985;4:337–44.

    CAS  Article  Google Scholar 

  9. 9.

    Aigner M, Feulner J, Schaffer S, Kischel R, Kufer P, Schneider K, et al. T lymphocytes can be effectively recruited for ex vivo and in vivo lysis of AML blasts by a novel CD33/CD3-bispecific BiTE antibody construct. Leukemia. 2013;27:1107–15.

    CAS  Article  Google Scholar 

  10. 10.

    Arndt C, Feldmann A, von Bonin M, Cartellieri M, Ewen EM, Koristka S, et al. Costimulation improves the killing capability of T cells redirected to tumor cells expressing low levels of CD33: description of a novel modular targeting system. Leukemia. 2014;28:59–69.

    CAS  Article  Google Scholar 

  11. 11.

    Friedrich M, Henn A, Raum T, Bajtus M, Matthes K, Hendrich L, et al. Preclinical characterization of AMG 330, a CD3/CD33-bispecific T-cell-engaging antibody with potential for treatment of acute myelogenous leukemia. Mol Cancer Ther. 2014;13:1549–57.

    CAS  Article  Google Scholar 

  12. 12.

    Krupka C, Kufer P, Kischel R, Zugmaier G, Bögeholz J, Köhnke T, et al. CD33 target validation and sustained depletion of AML blasts in long-term cultures by the bispecific T-cell-engaging antibody AMG 330. Blood. 2014;123:356–65.

    CAS  Article  Google Scholar 

  13. 13.

    Reusch U, Harrington KH, Gudgeon CJ, Fucek I, Ellwanger K, Weichel M, et al. Characterization of CD33/CD3 tetravalent bispecific tandem diabodies (TandAbs) for the treatment of acute myeloid leukemia. Clin Cancer Res. 2016;22:5829–38.

    CAS  Article  Google Scholar 

  14. 14.

    Mortland L, Alonzo TA, Walter RB, Gerbing RB, Mitra AK, Pollard JA, et al. Clinical significance of CD33 nonsynonymous single-nucleotide polymorphisms in pediatric patients with acute myeloid leukemia treated with gemtuzumab-ozogamicin-containing chemotherapy. Clin Cancer Res. 2013;19:1620–7.

    CAS  Article  Google Scholar 

  15. 15.

    Bacac M, Fauti T, Sam J, Colombetti S, Weinzierl T, Ouaret D, et al. A novel carcinoembryonic antigen T-cell bispecific antibody (CEA TCB) for the treatment of solid tumors. Clin Cancer Res. 2016;22:3286–97.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This research was funded in part through a sponsored research agreement from Covagen (to RBW). RBW is a Leukemia and Lymphoma Society Scholar in Clinical Research.

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Simon Brack or Roland B. Walter.

Ethics declarations

Conflict of interest

KK, VB, RS, JD, RS, DS, EK, AZ, IA-T, UvdB, SK-F, FD, WL, CA, SW, LD, JB, and SB are employees of Covagen AG. DS and RWH are employees of Janssen R&D. RBW received laboratory research grants and/or clinical trial support from Actinium Pharmaceuticals, Inc., Amgen Inc., Amphivena Therapeutics, Inc., Aptevo Therapeutics, Inc., Covagen AG, and Seattle Genetics, Inc.; has ownership interests with Amphivena Therapeutics, Inc.; and is (or has been) a consultant to Amphivena Therapeutics, Inc., Boehringer Ingelheim Pharma GmbH & Co. KG, Covagen AG, Emergent Biosolutions, Inc. (now Aptevo Therapeutics, Inc.), Pfizer, Inc., and Seattle Genetics, Inc. GSL and CJG declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Klupsch, K., Baeriswyl, V., Scholz, R. et al. COVA4231, a potent CD3/CD33 bispecific FynomAb with IgG-like pharmacokinetics for the treatment of acute myeloid leukemia. Leukemia 33, 805–808 (2019). https://doi.org/10.1038/s41375-018-0249-z

Download citation

Further reading

Search

Quick links