| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Recombinant Antibody Research Group,
Department of Tumor Progression and Immune Defense,
Department of Experimental Radiology, and
§
Department of Molecular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany
The use of anti-CD3 x antitumor bispecific Abs is an
attractive and highly specific approach in cancer therapy. Recombinant
Ab technology now provides powerful tools to enhance the potency of
such immunotherapeutic constructs. We designed a heterodimeric diabody
specific for human CD19 on B cells and CD3
chain of the TCR complex.
After production in Escherichia coli and purification,
we analyzed its affinity, stability, and pharmacokinetics, and tested
its capacity to stimulate T cell proliferation and mediate in vitro
lysis of CD19+ tumor cells. The effect of the diabody on
tumor growth was investigated in an in vivo model using immunodeficient
mice bearing a human B cell lymphoma. The CD3 x CD19 diabody
specifically interacted with both CD3- and CD19-positive cells, was
able to stimulate T cell proliferation in the presence of tumor cells,
and induced the lysis of CD19+ cells in the presence of
activated human PBL. The lytic potential of the diabody was enhanced in
the presence of an anti-CD28 mAb. In vivo experiments indicated a
higher stability and longer blood retention of diabodies compared with
single chain Fv fragments. Treatment of immunodeficient mice bearing B
lymphoma xenografts with the diabody and preactivated human PBL
efficiently inhibited tumor growth. The survival time was further
prolonged by including the anti-CD28 mAb. The CD3 x CD19
diabody is a powerful tool that should facilitate the immunotherapy of
minimal residual disease in patients with B cell leukemias and
malignant lymphomas.
This article has been cited by other articles:
|
|
 |
|
  D. Muller, A. Karle, B. Meissburger, I. Hofig, R. Stork, and R. E. Kontermann Improved Pharmacokinetics of Recombinant Bispecific Antibody Molecules by Fusion to Human Serum Albumin J. Biol. Chem., April 27, 2007; 282(17): 12650 - 12660. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Yan, M. J. Wolff, J. Unternaehrer, I. Mellman, and M. J. Mamula Targeting antigen to CD19 on B cells efficiently activates T cells Int. Immunol., July 1, 2005; 17(7): 869 - 877. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Le Gall, U. Reusch, M. Little, and S. M. Kipriyanov Effect of linker sequences between the antibody variable domains on the formation, stability and biological activity of a bispecific tandem diabody Protein Eng. Des. Sel., April 1, 2004; 17(4): 357 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Dreier, P. A. Baeuerle, I. Fichtner, M. Grun, B. Schlereth, G. Lorenczewski, P. Kufer, R. Lutterbuse, G. Riethmuller, P. Gjorstrup, et al. T Cell Costimulus-Independent and Very Efficacious Inhibition of Tumor Growth in Mice Bearing Subcutaneous or Leukemic Human B Cell Lymphoma Xenografts by a CD19-/CD3- Bispecific Single-Chain Antibody Construct J. Immunol., April 15, 2003; 170(8): 4397 - 4402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Kipriyanov, B. Cochlovius, H. J. Schafer, G. Moldenhauer, A. Bahre, F. Le Gall, S. Knackmuss, and M. Little Synergistic Antitumor Effect of Bispecific CD19 x CD3 and CD19 x CD16 Diabodies in a Preclinical Model of Non-Hodgkin's Lymphoma J. Immunol., July 1, 2002; 169(1): 137 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Cavacini, M. Duval, J. P. Eder, and M. R. Posner Evidence of Determinant Spreading in the Antibody Responses to Prostate Cell Surface Antigens in Patients Immunized with Prostate-specific Antigen Clin. Cancer Res., February 1, 2002; 8(2): 368 - 373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Cochlovius, S. M. Kipriyanov, M. J. J. G. Stassar, J. Schuhmacher, A. Benner, G. Moldenhauer, and M. Little Cure of Burkitt's Lymphoma in Severe Combined Immunodeficiency Mice by T Cells, Tetravalent CD3 CD19 Tandem Diabody, and CD28 Costimulation Cancer Res., August 1, 2000; 60(16): 4336 - 4341. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
