Abstract
TRU-016, under development by Trubion Pharmaceuticals Inc and Facet Biotech Corp, is an intravenously administered anti-CD37 IgG fusion protein for the potential treatment of B-cell malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), as well as for autoimmune and inflammatory diseases. TRU-016 was created by humanizing SMIP-016, a mouse/human chimeric protein that demonstrated antitumor activity against lymphoid malignancies in preclinical studies, including in human B-cell tumor mouse xenograft models. In addition, TRU-016 demonstrated synergistic or additive activity in NHL cells in combination with rituximab, rapamycin, doxorubicin and bendamustine. In a phase I/II clinical trial in refractory or relapsed patients with CLL or small lymphocytic lymphoma, TRU-016 was well tolerated, with clinical benefit and a reduced absolute lymphocyte count observed in all cohorts dosed at > 0.1 mg/kg. TRU-016 is a promising therapeutic agent for patients with B-cell lymphoid malignancies, especially patients refractory to standard treatment.
MeSH terms
-
Animals
-
Antigens, CD / immunology*
-
Antigens, Neoplasm / immunology*
-
Antineoplastic Agents / adverse effects
-
Antineoplastic Agents / immunology
-
Antineoplastic Agents / therapeutic use*
-
Antineoplastic Combined Chemotherapy Protocols / pharmacology
-
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
-
Autoimmune Diseases / drug therapy
-
Autoimmune Diseases / immunology
-
Clinical Trials as Topic
-
Drug Evaluation, Preclinical
-
Humans
-
Immunoglobulin G / adverse effects
-
Immunoglobulin G / immunology
-
Immunoglobulin G / therapeutic use*
-
Inflammation / drug therapy
-
Inflammation / immunology
-
Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
-
Leukemia, Lymphocytic, Chronic, B-Cell / immunology
-
Lymphoma, B-Cell / drug therapy*
-
Lymphoma, B-Cell / immunology
-
Mice
-
Recombinant Fusion Proteins / adverse effects
-
Recombinant Fusion Proteins / immunology
-
Recombinant Fusion Proteins / therapeutic use*
-
Tetraspanins
Substances
-
Antigens, CD
-
Antigens, Neoplasm
-
Antineoplastic Agents
-
CD37 protein, human
-
Immunoglobulin G
-
Recombinant Fusion Proteins
-
TRU 016
-
Tetraspanins