The Generation and Anti-Myeloma Activity of a Chimeric Anti-CD54 Antibody, cUV3

Smallshaw, Joan E.; Coleman, Elaine J.; Spiridon, Camelia; Vitetta, Ellen S.

doi:10.1097/00002371-200411000-00001

Cited by 10 publications

(4 citation statements)

References 28 publications

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“…Like rituximab, anti-CD70 and anti-CD54 (c-CUV3) are chimaeric mAbs that could prove to be effective agents with further clinical development, by interfering with regulation of antigen-primed B-cell differentiation, and blocking the interaction between CD54 and leucocyte function-associated antigen, respectively (Smallshaw et al, 2004;Bringhen et al, 2006;Coleman et al, 2006;McEarchern et al, 2007). A humanized variant of anti-CD70 mAB also shows potent anti-MM activity (McEarchern et al, 2005).…”

Section: Chimaeric Antibodiesmentioning

confidence: 99%

Anti‐CD20 monoclonal antibody therapy in multiple myeloma

et al. 2008

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SummaryCD20 is a particularly appealing target that is expressed on the surface of almost all B cells, with no significant shedding, secretion or internalization. In contrast to the demonstrated efficacy of anti-CD20 strategies in various B-cell lymphoproliferative disorders, the role of such therapy in multiple myeloma is undetermined and controversial. The expression of CD20 by myeloma cells is heterogeneous, and can be detected only in 13-22% of patients. However, there is increasing interest in testing anti-CD20 therapy in myeloma because of recent studies suggesting the existence of clonogenic CD20-positive precursor B cells in the disease. This article reviews the rationale, preclinical and clinical activity of anti-CD20 therapy in myeloma. Clinical trials show that anti-CD20 therapy with rituximab elicits a partial response in approximately 10% of CD20 + patients with multiple myeloma. In addition, there is preliminary evidence of disease stabilization in 50-57% of CD20 + patients for a period of 10-27 months. Further largescale clinical trials are therefore needed to establish the role of this promising strategy in the treatment of myeloma.

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Section: Chimaeric Antibodiesmentioning

confidence: 99%

Anti‐CD20 monoclonal antibody therapy in multiple myeloma

et al. 2008

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“…30 However, OCM3 cells were poor targets for ADCC. In 4 experiments in which OCM3 cells were used as targets and BALB/c splenocytes as effectors at a ratio of 100:1, the specific killing relative to the control was 4.5% (data not shown).…”

Section: Ocm3 Cells Are Poor Targets For Adcc In Vitromentioning

confidence: 99%

Effect of an anti‐CD54 (ICAM‐1) monoclonal antibody (UV3) on the growth of human uveal melanoma cells transplanted heterotopically and orthotopically in SCID mice

Wang

Coleman

Pop

et al. 2005

Intl Journal of Cancer

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We have shown that administration of a novel anti-CD54 monoclonal antibody (UV3) results in long-term survival of SCID mice bearing human myeloma xenografts. Previous studies have demonstrated a link between the expression of CD54 and the progression of uveal melanoma. Our study assessed the expression of CD54 on 7 human uveal melanoma cell lines and 3 cell lines established from uveal melanoma metastases. In vivo studies examined the efficacy of systemic and local administration of UV3 antibody on the progression of uveal melanoma cells transplanted either heterotopically or orthotopically into SCID mice. Five of the 7 primary uveal melanoma cell lines and all 3 of the metastases cell lines expressed CD54. Intraperitoneal injection of either IgG or F(ab 0 ) 2 fragments of UV3 significantly inhibited the growth of subcutaneous and intraocular melanomas. Subconjunctival injection of either IgG or F(ab 0 ) 2 fragments of UV3 produced a significant reduction in the growth of intraocular melanomas, even if the antibody was administered after the appearance of intraocular tumors. The results indicate that both primary and metastatic human uveal melanoma cells express CD54. The marked inhibition of intraocular and subcutaneous uveal melanoma progression suggests that UV3 antibody is a promising therapeutic agent for further evaluation in patients with uveal melanoma. This is especially noteworthy, as no existing therapeutic modality prevents metastasis of uveal melanoma or prolongs the survival of patients with uveal melanoma. ' 2005 Wiley-Liss, Inc.Key words: anterior chamber; eye; CD54; immunotherapy; uveal melanoma Uveal melanoma is the most common intraocular malignancy in adults and occurs with a frequency of 6 to 7 cases per one million adults. 1 Although cutaneous and uveal melanomas share a neural crest origin, they differ significantly in their epidemiological, 2 cytogenetic 3 , metastatic 4-6 and immunological 4 characteristics. One of the remarkable differences between cutaneous and uveal melanomas is their metastatic behavior. Although skin melanomas metastasize to almost any organ, uveal melanoma displays a propensity to spread to the liver. Indeed, liver metastases are present in up to 95% of the patients who die from uveal melanomas. [7][8][9][10] Although there have been advances in the treatment of primary uveal melanomas, the 5-year survival rate for uveal melanoma patients has not improved in the past 30 years. 1,10 Moreover, no therapeutic modality prevents the metastasis of uveal melanoma or prolongs the survival of patients. 11 Studies have suggested a correlation between the expression of CD54 and the progression of skin and uveal melanomas. 12,13 Expression of CD54 was detected in 81-85% of human uveal melanoma specimens. 13,14 Reduced expression of CD54 in primary uveal melanomas has been associated with increased metastatic disease. 13 CD54 is an important ligand for leukocytes and is believed to be involved in immune surveillance. 15,16 Intravenous administration of MAb against human CD54 (U...

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“…Experimental results indicating suppression of tumors after the administration of anti-CD54 antibody seem to support this notion. 12,13 However, the possibility of CD54-mediated apoptosis of tumor cells has not been extensively discussed, and moreover, the relevant molecular biologic mechanisms have yet to be clarified. Several studies have confirmed MAP kinase activation in various tumor cells by stimulation of CD54 and thus have attempted to explain the formation of reactive oxygen species (ROS) and the increase in Ca 2+ influx.…”

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confidence: 99%

Cross-linking of CD54 on Burkitt Lymphoma Cell Line Raji and Ramos Induces FasL Expression by Reactive Oxygen Species and Apoptosis of Adjacent Cells in Fas/FasL Interaction

Kim¹,

Park²,

Song³

et al. 2007

Journal of Immunotherapy

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CD54 is a cell surface adhesive glycoprotein, which is expressed in most cells. Interaction between CD54 and its ligands is involved in several cellular events including activation, proliferation, and cell death and also cell-to-cell adhesion. In the present study, we found that cross-linking of CD54 on Burkitt lymphoma cell lines, Raji and Ramos, induced apoptosis. We investigated that cross-linking of CD54 on Raji and Ramos using immobilized anti-CD54 mAb (clone 6.5B5) leads to apoptosis. CD54-induced apoptosis took place in association with an increase of intracellular reactive oxygen species (ROS) and a loss of the mitochondrial membrane potential and also the activation of caspases 3 and 9, resulting in the degradation of the proteolytic poly (ADP-ribose) polymerase. Pretreatment of each N-acetyl cystein and N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (a broad caspase inhibitor) blocked apoptosis. Cross-linking of CD54 immediately induced expression of fasL, which was inhibited by pretreatment of N-acetyl cystein. NOK-1 (antagonistic anti-fasL), ZB4 (antagonistic anti-fas), and N-benzyloxycarbonyl-Ile-Glu-Thr-Asp-fluoromethylketon (caspase 8 inhibitor) effectively rescued cells from apoptosis via adjacent fas-fasL interaction but did not block ROS generation. Taken together, it is concluded that engagement of CD54 on B lymphoma cell lines by anti-CD54 mAb may trigger fasL expression through ROS generation and may subsequently induce apoptosis in adjacent fas-fasL interaction.

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The Generation and Anti-Myeloma Activity of a Chimeric Anti-CD54 Antibody, cUV3

Cited by 10 publications

References 28 publications

Anti‐CD20 monoclonal antibody therapy in multiple myeloma

Anti‐CD20 monoclonal antibody therapy in multiple myeloma

Effect of an anti‐CD54 (ICAM‐1) monoclonal antibody (UV3) on the growth of human uveal melanoma cells transplanted heterotopically and orthotopically in SCID mice

Cross-linking of CD54 on Burkitt Lymphoma Cell Line Raji and Ramos Induces FasL Expression by Reactive Oxygen Species and Apoptosis of Adjacent Cells in Fas/FasL Interaction

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