Phase 1 study of TRU-015, a CD20-directed small modular immunopharmaceutical (SMIP™) protein therapeutic, in subjects with rheumatoid arthritis

Burge, Daniel; Bookbinder, SA; Kivitz, A.; Fleischmann, R; Shu, Cathye; Bannink, Jeannette; Barone, D.

doi:10.1186/ar2257

Cited by 4 publications

(4 citation statements)

References 3 publications

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“…51 Preliminary results of the first phase I study with Tru15 demonstrated it to be clinically well tolerated, and successful at depleting B-cells in a dose-dependent manner with an extended serum half-life (12-19 days). 52 Thus, development of CD37-SMIP for clinical investigation in CLL based on our data herein represents an obvious extension of this exciting targeted therapeutic class of agents directed at a B-cellselective antigen not yet pursued. The unique engineered features of SMIP-based therapies may offer an advantage over classic antibody based-therapies, including improved effector function, target affinity, and apoptotic signaling.…”

Section: Discussionmentioning

confidence: 93%

Targeting CD37-positive lymphoid malignancies with a novel engineered small modular immunopharmaceutical

Zhao

Lapalombella²,

Joshi³

et al. 2007

Blood

124

116

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CD37 is a lineage-specific B-cell antigen that to date has been neglected as an attractive therapeutic target. To exploit this, novel CD37-specific small modular immunopharmaceuticals ( IntroductionImmunotherapy using monoclonal antibodies (MAbs) is emerging as a safe and selective method for the treatment of cancer. 1 The role of monoclonal antibodies in B-cell malignancies has expanded since the introduction of rituximab (Rituxan) targeted against the CD20 antigen on the B-cell surface in 1997. Numerous studies have confirmed the efficacy of rituximab as a single agent and in combination therapy in low-grade non-Hodgkin lymphoma (NHL), 2-6 mantle-cell lymphoma, 7-11 diffuse large-cell lymphoma, 12,13 and Burkitt leukemia/lymphoma. 14 However, only a subset of patients respond to therapy and the majority of those eventually relapse after rituximab treatment. Therefore, identification of new therapeutic targets on B cells that are potentially more effective than CD20 represents a novel strategy for therapy of B-cell malignancies.The CD37 antigen is one potential target that has not been adequately evaluated. CD37 is a heavily glycosylated 40-to 52-kDa glycoprotein and a member of the tetraspan transmembrane family of proteins. 15,16 CD37 is expressed strongly on the surface of B cells and transformed mature B-cell leukemia and lymphoma cells [17][18][19][20]22,23,25,26 but is either absent or minimally expressed on normal T cells. 21 The CD37 antigen is expressed on monocytes and granulocytes at very low density and is absent on natural killer (NK) cells, platelets, and erythrocytes. 15,22 During B-cell development, CD37 is expressed in cells progressing from pre-B to peripheral mature B-cell stages and is absent on terminal differentiation to plasma cells. 23 Although the precise function of CD37 remains unknown, it has been found to form complexes with CD53, CD81, CD82, and class II glycoprotein on B-cell surface that may represent an ion channel or a transporter. 24 CD37 has modest internalization and shedding in transformed B cells expressing the antigen. 25,26 It is highly expressed in endosomes and exosomes in B lymphocytes, reflecting possible involvement in intracellular trafficking and antigen presentation. 15 Targeted inactivation of CD37 in mice revealed no changes in the development of lymphoid organs but a reduced IgG1 level in the sera and an alteration of response to T-cell-dependent antigens, indicating a possible role of CD37 in T cell-B cell interaction. 27 Given the relative B-cell selectivity, CD37 thus represents a valuable therapeutic target for malignancies derived from peripheral mature B cells, such as B-cell chronic lymphocytic leukemia (CLL), hairy-cell leukemia (HCL), and B-cell NHL. 25,26 In particular, CLL may be a good target of CD37-based immunotherapy, because the expression of CD37 is relatively high, even compared with CD20, in this type of leukemia. 17 Efforts to target CD37 clinically have been limited. One reported preclinical trial performed in the late 1980s examined the ...

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Section: Discussionmentioning

confidence: 93%

Targeting CD37-positive lymphoid malignancies with a novel engineered small modular immunopharmaceutical

Zhao

Lapalombella²,

Joshi³

et al. 2007

Blood

124

116

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“…Decreases in peripheral B cell counts were observed in all dose groups at the first time-point after drug administration. The overall mean half-life of TRU-015 was 295 h [23 ].…”

Section: Clinical Validationmentioning

confidence: 99%

Biopharmaceutical drug discovery using novel protein scaffolds

Gill¹,

Damle²

2006

Current Opinion in Biotechnology

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“…Therefore, the clinical relevance further will need to be investigation. TRU-015 ((CytoxB20G) is a single chain anti- CD20 molecule that is a small modular immuno-pharmaceutical drug composed of human IgG1 Fc and CH2 and CH3 hinge regions which linked directly to an anti-CD20 specific Fv regions [ 70 – 72 ]. It has high ADCC and low CDC activating potential.…”

Section: Development Of Novel Anti-cd20 Mabsmentioning

confidence: 99%

Development of Novel Anti-Cd20 Monoclonal Antibodies and Modulation in Cd20 Levels on Cell Surface: Looking to Improve Immunotherapy Response

Singh

Gupta

2015

J Cancer Sci Ther

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Rituximab has been revolutionized and validated CD20 targeting monoclonal antibody. Although, it is widely used for lymphoma therapy and many patients have been benefited. However significant numbers of patients are refractory or developed resistance to current therapies due to low level of CD20 expression and/or availability on cells surface. Thus development of novel anti-CD20 mAbs with great cell killing ability and enhance CD20 levels on cell surface can potentially exploit lymphoma therapy. In this scenario, we are summarizing the recently developed mAbs against CD20 and compounds that have ability to induce CD20 expression at significant level. We also are providing information regarding combination strategy for use of radiation and anti-CD20 mAbs in vitro. However, it will need to be determined by rigorous at pre-clinical and clinic testing. We hope this review will be beneficial for current research in the area of immunotherapy or radio-immunotherapy.

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Phase 1 study of TRU-015, a CD20-directed small modular immunopharmaceutical (SMIP™) protein therapeutic, in subjects with rheumatoid arthritis

Cited by 4 publications

References 3 publications

Targeting CD37-positive lymphoid malignancies with a novel engineered small modular immunopharmaceutical

Targeting CD37-positive lymphoid malignancies with a novel engineered small modular immunopharmaceutical

Biopharmaceutical drug discovery using novel protein scaffolds

Development of Novel Anti-Cd20 Monoclonal Antibodies and Modulation in Cd20 Levels on Cell Surface: Looking to Improve Immunotherapy Response

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