Preclinical evaluation of an anti-CD25 monoclonal antibody, 7G7/B6, armed with the beta-emitter, yttrium-90, as a radioimmunotherapeutic agent for treating lymphoma.

OBJECTIVE Radioimmunotherapy of cancer with radiolabeled antibodies has shown promise. We evaluated an anti-CD25 monoclonal Antibody, 7G7/B6, armed with (90)Y as a potential radioimmunotherapeutic agent for CD25-expressing lymphomas. MATERIALS AND METHODS The lymphoma model was established by subcutaneous injection of 1 x 10(7) SUDHL-1 cells into nude mice. The biodistribution of (111)In-7G7/B6 and therapeutic studies with (90)Y-7G7/B6 were performed in the tumor-bearing mice. RESULTS Therapy using (90)Y-7G7/B6 prolonged survival of the SUDHL-1 lymphoma-bearing mice significantly, as compared with either untreated mice or the mice treated with (90)Y-11F11, a radiolabeled isotype-matched control antibody (p < 0.001). All of the mice in the control and the (90)Y-11F11 treatment groups died by days 18 and 24, respectively. In contrast, 30% of the mice in the low-dose group (75 microCi of (90)Y-7G7/B6/mouse) and 75% in the high-dose group (150 microCi of (90)Y-7G7/B6/mouse) became tumor free and remained healthy for greater than 6 months. CONCLUSIONS Our findings suggested that (90)Y-7G7/B6 is a potentially useful radioimmunotherapeutic agent for the treatment of patients with CD25-expressing lymphomas.

[1]  T. Waldmann,et al.  The anti-CD25 monoclonal antibody 7G7/B6, armed with the alpha-emitter 211At, provides effective radioimmunotherapy for a murine model of leukemia. , 2006, Cancer research.

[2]  T. Waldmann,et al.  Effective treatment of a murine model of adult T-cell leukemia using 211At-7G7/B6 and its combination with unmodified anti-Tac (daclizumab) directed toward CD25. , 2006, Blood.

[3]  T. Waldmann.  Effective cancer therapy through immunomodulation. , 2006, Annual review of medicine.

[4]  T. Waldmann,et al.  Combination therapy for adult T-cell leukemia-xenografted mice: flavopiridol and anti-CD25 monoclonal antibody. , 2005, Blood.

[5]  W. Wilson,et al.  Elevated serum-soluble interleukin-2 receptor levels in patients with anaplastic large cell lymphoma. , 2004, Blood.

[6]  T. Waldmann,et al.  Activating Fc Receptors Are Required for Antitumor Efficacy of the Antibodies Directed toward CD25 in a Murine Model of Adult T-Cell Leukemia , 2004, Cancer Research.

[7]  M. Brechbiel,et al.  Antibody-targeted radiation cancer therapy , 2004, Nature Reviews Drug Discovery.

[8]  T. Waldmann.  ABCs of Radioisotopes Used for Radioimmunotherapy: α- and β-Emitters , 2003 .

[9]  T. Waldmann,et al.  Immunotherapy: past, present and future , 2003, Nature Medicine.

[10]  T. Waldmann,et al.  Pretarget radiotherapy with an anti-CD25 antibody-streptavidin fusion protein was effective in therapy of leukemia/lymphoma xenografts , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[11]  T. Waldmann.  ABCs of radioisotopes used for radioimmunotherapy: alpha- and beta-emitters. , 2003, Leukemia and Lymphoma.

[12]  T. Waldmann,et al.  Radioimmunotherapy of A431 xenografted mice with pretargeted B3 antibody-streptavidin and (90)Y-labeled 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)-biotin. , 2002, Cancer research.

[13]  J. Humm,et al.  Targeted α particle immunotherapy for myeloid leukemia , 2002 .

[14]  Richard J Lee,et al.  Flavopiridol and trastuzumab synergistically inhibit proliferation of breast cancer cells: association with selective cooperative inhibition of cyclin D1-dependent kinase and Akt signaling pathways. , 2002, Molecular cancer therapeutics.

[15]  T. Waldmann,et al.  Pretargeting radioimmunotherapy of a murine model of adult T-cell leukemia with the alpha-emitting radionuclide, bismuth 213. , 2002, Blood.

[16]  L. Chappell,et al.  In vivo comparison of macrocyclic and acyclic ligands for radiolabeling of monoclonal antibodies with 177Lu for radioimmunotherapeutic applications. , 2002, Nuclear medicine and biology.

[17]  T. Waldmann,et al.  Proteasome inhibitor PS-341, a potential therapeutic agent for adult T-cell leukemia. , 2002, Cancer research.

[18]  B. E. C. Oiffier,et al.  CHOP Chemotherapy plus Rituximab Compared with CHOP Alone in Elderly Patients with Diffuse Large-B-Cell Lymphoma , 2002 .

[19]  J. Humm,et al.  Targeted alpha particle immunotherapy for myeloid leukemia. , 2002, Blood.

[20]  Pierre Morel,et al.  CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. , 2002, The New England journal of medicine.

[21]  D. Scheinberg,et al.  Tumor Therapy with Targeted Atomic Nanogenerators , 2001, Science.

[22]  T. Waldmann,et al.  Comparative cellular catabolism and retention of astatine-, bismuth-, and lead-radiolabeled internalizing monoclonal antibody. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[23]  T. Fleming,et al.  Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. , 2001, The New England journal of medicine.

[24]  T. Waldmann,et al.  IL-2Ralpha-Directed monoclonal antibodies provide effective therapy in a murine model of adult T-cell leukemia by a mechanism other than blockade of IL-2/IL-2Ralpha interaction. , 2000, Cancer research.

[25]  T. Waldmann,et al.  Advances in interleukin 2 receptor targeted treatment , 2000, Annals of the rheumatic diseases.

[26]  J. Humm,et al.  Radioimmunotherapy with alpha-emitting nuclides , 1998, European Journal of Nuclear Medicine.

[27]  I. Pastan,et al.  Evaluation of the in vivo biodistribution of yttrium-labeled isomers of CHX-DTPA-conjugated monoclonal antibodies. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[28]  T. Waldmann,et al.  Radioimmunotherapy of interleukin-2R alpha-expressing adult T-cell leukemia with Yttrium-90-labeled anti-Tac. , 1995, Blood.

[29]  H. Sakahara,et al.  Radioimmunoimaging of colon cancer xenografts with anti-Tn monoclonal antibody. , 1995, Nuclear medicine and biology.

[30]  T. Waldmann,et al.  The interleukin-2 receptor: a target for monoclonal antibody treatment of human T-cell lymphotrophic virus I-induced adult T-cell leukemia. , 1993, Blood.

[31]  A. O’Brien,et al.  Isolation and characterization of monoclonal antibodies to Shiga-like toxin II of enterohemorrhagic Escherichia coli and use of the monoclonal antibodies in a colony enzyme-linked immunosorbent assay , 1988, Journal of clinical microbiology.

[32]  C. Coleman,et al.  Radioimmunotherapy with alpha-particle-emitting immunoconjugates. , 1988, Science.

[33]  D. Nelson,et al.  A monoclonal antibody 7G7/B6, binds to an epitope on the human interleukin-2 (IL-2) receptor that is distinct from that recognized by IL-2 or anti-Tac. , 1985, Hybridoma.