PUBLICAÇÕES científicas

Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment

Seckinger A (1), Delgado JA (2), Moser S (3), Moreno L (2), Neuber B 4, Grab A (1), Lipp S (1), Merino J (2), Prosper F (2), Emde M (1), Delon C (3), Latzko M (3), Gianotti R (3), Lüoend R (3), Murr R (3), Hosse RJ (3), Harnisch LJ (3), Bacac M (3), Fauti T (3), Klein C (3), Zabaleta A (2), Hillengass J (4), Cavalcanti-Adam EA (5), Ho AD (4), Hundemer M (4), San Miguel JF (2), Strein K (6), Umaña P (3), Hose D (7), Paiva B (8), Vu MD (9). (1) Universitätsklinikum Heidelberg, Labor für Myelomforschung and Medizinische Klinik V, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
(2) Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, IDISNA, Avda. Pío XII, 55, 31008 Pamplona, Spain.
(3) Roche Innovation Center Zurich, 8952 Schlieren, Switzerland.
(4) Universitätsklinikum Heidelberg, Medizinische Klinik V, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
(5) University of Heidelberg, Institute for Physical Chemistry and Max Planck Institute for Medical Research, 69120 Heidelberg, Germany.
(6) EngMab AG, 8808 Pfäffikon, Switzerland.
(7) Universitätsklinikum Heidelberg, Labor für Myelomforschung and Medizinische Klinik V, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
(8) Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada, IDISNA, Avda. Pío XII, 55, 31008 Pamplona, Spain.
(9) EngMab AG, 8808 Pfäffikon, Switzerland.

Revisão:Cancer Cell

Data: 13/Mar/2017

Hematología y Hemoterapia [ES]

RESUMO

We identified B cell maturation antigen (BCMA) as a potential therapeutic target in 778 newly diagnosed and relapsed myeloma patients.

We constructed an IgG-based BCMA-T cell bispecific antibody (EM801) and showed that it increased CD3+ T cell/myeloma cell crosslinking, followed by CD4+/CD8+ T cell activation, and secretion of interferon-γ, granzyme B, and perforin.

This effect is CD4 and CD8 T cell mediated. EM801 induced, at nanomolar concentrations, myeloma cell death by autologous T cells in 34 of 43 bone marrow aspirates, including those from high-risk patients and patients after multiple lines of treatment, tumor regression in six of nine mice in a myeloma xenograft model, and depletion of BCMA+ cells in cynomolgus monkeys.

Pharmacokinetics and pharmacodynamics indicate weekly intravenous/subcutaneous administration.

CITAÇÃO DO ARTIGO  Cancer Cell. 2017 Mar 13;31(3):396-410. doi: 10.1016/j.ccell.2017.02.002

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