Redirection of T cells with a first fully humanized bispecific CD33-CD3 antibody efficiently eliminates AML blasts without harming hematopoietic stem cells

Leukemia

Volumn 27, Issue 4, 2013, Pages 964-967

  Arndt, C ^a   Von Bonin, M ^b   Cartellieri, M ^a   Feldmann, A ^a   Koristka, S ^a   Michalk, I ^a   Stamova, S ^a   Bornhauser M ^b   Schmitz, M ^a,c   Ehninger, G ^b   Bachmann, M ^a,c  

^a DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^b UNIVERSITY HOSPITAL CARL GUSTAV CARUS   (Germany)

^c CENTER FOR REGENERATIVE THERAPIES DRESDEN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CD33 ANTIGEN; CD34 ANTIGEN; MONOCLONAL ANTIBODY CD3;

ACUTE GRANULOCYTIC LEUKEMIA; CANCER PATIENT; CELL ISOLATION; CHIMERA; CYTOLYSIS; DRUG TARGETING; FLOW CYTOMETRY; HEMATOPOIETIC STEM CELL; HUMAN; IN VIVO STUDY; LETTER; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN;

ANTIBODIES, BISPECIFIC; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTIGENS, CD3; FLOW CYTOMETRY; HEMATOPOIETIC STEM CELLS; HUMANS; LEUKEMIA, MYELOID, ACUTE; SIALIC ACID BINDING IG-LIKE LECTIN 3; T-LYMPHOCYTES;

EID: 84876099903     PISSN: 08876924     EISSN: 14765551     Source Type: Journal    
DOI: 10.1038/leu.2013.18     Document Type: Letter

References (14)

1. Robak T, Wierzbowska A. Current and emerging therapies for acute myeloid leukemia. Clin Ther 2009; 31: 2349-2370.
2. Dinndorf PA, Andrews RG, Benjamin D, Ridgway D, Wolff L, Bernstein ID. Expression of normal myeloid-associated antigens by acute leukemia cells. Blood 1986; 67: 1048-1053.
3. Hauswirth AW, Florian S, Printz D, Sotlar K, Krauth MT, Fritsch G et al. Expression of the target receptor CD33 in CD34\+/CD38-/CD123\+ AML stem cells. Eur J Clin Invest 2007; 37: 73-82.
4. Horton SJ, Huntly BJ. Recent advances in acute myeloid leukemia stem cell biology. Haematologica 2012; 97: 966-974.
5. Walter RB, Appelbaum FR, Estey EH, Bernstein ID. Acute myeloid leukemia stem cells and CD33-targeted immunotherapy. Blood 2012; 119: 6198-6208.
6. 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(s) antibody construct. Leukemia 2012; e-pub ahead of print 14 December 2012; doi:10.1038/leu.2012.341.
7. Taussig DC, Pearce DJ, Simpson C, Rohatiner AZ, Lister TA, Kelly G et al. Hematopoietic stem cells express multiple myeloid markers: implications for the origin and targeted therapy of acute myeloid leukemia. Blood 2005; 106: 4086-4092.
8. Stamova S, Cartellieri M, Feldmann A, Arndt C, Koristka S, Bartsch H et al. Unexpected recombinations in single chain bispecific anti-CD3-anti-CD33 antibodies can be avoided by a novel linker module. Mol Immunol 2011; 49: 474-482.
9. Stamova S, Cartellieri M, Feldmann A, Bippes CC, Bartsch H, Wehner R et al. Simultaneous engagement of the activatory receptors NKG2D and CD3 for retargeting of effector cells to CD33-positive malignant cells. Leukemia 2011; 25: 1053-1056.
10. Feldmann A, Arndt C, Töpfer K, Stamova S, Krone F, Cartellieri M et al. Novel humanized and highly efficient bispecific antibodies mediate killing of prostate stem cell antigen-expressing tumor cells by CD8\+ and CD4\+ T cells. J Immunol 2012; 189: 3249-3459.
11. Koristka S, Cartellieri M, Theil A, Feldmann A, Arndt A, Stamova S et al. Retargeting of human regulatory T cells by single-chain bispecific antibodies. J Immunol 2012; 188: 1551-1558.
12. Dutour A, Marin V, Pizzitola I, Valsesia-Wittmann S, Lee D, Yvon E et al. In vitro and in vivo antitumor effect of anti-CD33 chimeric receptor-expressing EBV-CTL against CD33\+ acute myeloid leukemia. Adv Hematol 2012; 2012: 683065.
13. Robertson MJ, Soiffer RJ, Freedmann AA, Rabinowe SL, Anderson KC, Ervin TJ. Human bone marrow depleted of CD33-positive cells mediates delayed but durable reconstitution of hematopoiesis: clinical trial of MY9 monoclonal antibody-purged autografts for the treatment of acute myeloid leukemia. Blood 1992; 79: 2229-2236.
14. Jing D, Fonseca AV, Alakel N, Fierro FA, Muller K, Bornhauser M et al. Hematopoietic stem cells in co-culture with mesenchymal stromal cells-modeling the niche compartments in vitro. Haematologica 2010; 4: 542-550.