Expression of CD28 and CD40 in human myeloma cells: a comparative study with normal plasma cells

Pellat‐Deceunynck, Catherine; Bataille, Régis; Robillard, Nelly; Rapp, MJ; Morineau, N Juge-; Wijdenes, J; Amiot, Martine

doi:10.1182/blood.v84.8.2597.bloodjournal8482597

Cited by 41 publications

(41 citation statements)

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“…investigators (Pellat-Deceunynck et al, 1994;Tong et al, 1994;Pope et al, 2000). Nevertheless, we found that CD40 negative myeloma cells also could effect significantly greater proliferation in the MLR following infection with Ad-CD154, albeit less effectively than Ad-CD154-infected CD40 positive myeloma cells.…”

Section: Discussionmentioning

confidence: 64%

Adenovirus transduction to effect CD40 signalling improves the immune stimulatory activity of myeloma cells

2002

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Summary. Neoplastic plasma cells from patients with myeloma fail to stimulate an effective anti‐myeloma immune response, which may be in part due to their deficient expression of immune accessory molecules. Attempting to alter this, we infected myeloma cell lines and patient‐derived primary myeloma cells with an adenovirus encoding CD154 (Ad‐CD154). Myeloma cells were made to express the CD154 transgene at multiplicity of infection (MOI) between 10 and 1000. Furthermore, infection of CD40positive myeloma cells with Ad‐CD154, but not an adenovirus encoding an irrelevant transgene, β‐galactosidase (Ad‐LacZ), induced enhanced expression of immune accessory molecules, such as CD54, HLA‐DR and CD70. In addition, Ad‐CD154‐infected myeloma cells could activate bystander CD40positive antigen‐presentingcells to express immune accessory molecules. Consequently, Ad‐CD154 infected myeloma cells stimulated proliferation in allogeneic mixed lymphocyte reactions (MLR). Finally, co‐infection of CD40negative myeloma cells with Ad‐CD154 and an adenovirus encoding CD40 (Ad‐CD40) induced expression of immune accessory molecules and enhanced the MLR stimulatory capacity of transduced myeloma cells. Collectively, these results indicate that infection of myeloma cells with Ad‐CD154 or Ad‐CD154/Ad‐CD40 can induce changes in myeloma cells that enhance their ability to induce cellular immune activation. As such, this approach may have potential application for immune therapy of patients with this disease.

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Section: Discussionmentioning

confidence: 64%

Adenovirus transduction to effect CD40 signalling improves the immune stimulatory activity of myeloma cells

2002

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“…In contrast, FCM revealed that virtually all CD138 þþ PB cells were clonal cells. At present, BM and PB malignant PC have been detected by their high expression of CD38 [21]. However, CD38 is expressed on a large variety of other cells, including CD34 þ cells [43].…”

Section: Discussionmentioning

confidence: 99%

“…Malignant PB and BM plasma cells were detected using CD138 (B-B4)-FITC or -PE, a MoAb with high specificity against plasma cells, and CD38-FITC, -PE or -TC MoAbs. As has been previously reported, plasma cells were defined as CD38 þþ /CD138 þþ [21]. PE-or FITC-conjugated MoAbs against several adhesion molecules or B cell antigens were added to each sample.…”

Section: Flow Cytometrymentioning

confidence: 99%

Normal and clonal B lineage cells can be distinguished by their differential expression of B cell antigens and adhesion molecules in peripheral blood from multiple myeloma (MM) patients—diagnostic and clinical implications

Luque

Brieva

Moreno

et al. 1998

Clinical and Experimental Immunology

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SUMMARYHuman MM is a haematologic disorder characterized by the accumulation of malignant plasma cells (PC), primarily in the bone marrow (BM). Although these cells characteristically home to the BM, in recent years several groups have detected the presence of related malignant B cells in the peripheral blood (PB) which could be implicated in the progression and spread of the disease. However, the proportion and origin of these clonotypic circulating B cells is still controversial. In this study, using a triple-staining flow cytometric procedure and a whole blood lysis method, PB B lineage cells could be divided into two populations according to their distinct repertoires of cell adhesion molecules and B cell antigens in untreated MM patients. The results show that: (i) the percentage and the absolute number of PB CD19þ B cells were decreased in MM patients compared with controls; (ii) the quantity and percentage of B cell antigens (CD20, CD22, CD24, DR, CD138) and adhesion molecules (b 1 -and b 2 -integrins, CD44, CD54, CD56, CD61 and CD62L) expressed by these PB CD19 þ cells of MM patients and healthy subjects were similar and all of them were virtually polyclonal cells; (iii) a very minor circulating CD19 -CD38 þþ CD45 ¹/dim subset was also detected which expressed CD138 (B-B4) (high intensity), monoclonal cytoplasmic immunoglobulin (cIg), and was negative for pan-B antigens (CD19, CD20, CD24, DR), surface immunoglobulin (sIg) and several adhesion molecules such as CD62L, CD18 and CD11a; this CD19 -CD38 þþ CD45 -/dim CD138 þþ subset was not found in normal blood and exhibited a phenotypic profile which was closely related to that of malignant BM plasma cells, with the exception of the CD56 antigen. Polymerase chain reaction (PCR) analysis of IgH clonotypic rearrangements confirmed these results. We postulate that, in MM patients, circulating B lineage cells may be divided into two different categories: polyclonal CD19 þ B cells and a very minor proportion of clonal CD138 þþ PC that escape from the BM.

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“…CD40 is a member of the Tumour Necrosis Factor (TNF) receptor super family expressed as a type-I transmembrane protein (40 kDa) on both haematopoietic and non-haematopoietic tissues. CD40 is expressed on normal B-cells and at relatively high levels in most B cell malignancies including CLL (Banchereau et al, 1994;Pellat-Deceunynck et al, 1994;Wang et al, 1997). These findings together provide a rationale for targeting this antigen with therapeutic antibodies.…”

mentioning

confidence: 92%

The humanized CD40 antibody SGN‐40 demonstrates pre‐clinical activity that is enhanced by lenalidomide in chronic lymphocytic leukaemia

Lapalombella

Gowda

Joshi³

et al. 2009

Br J Haematol

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SummaryAntibody-based therapies, such as rituximab and alemtuzumab, have contributed significantly to the treatment of Chronic Lymphocytic leukaemia (CLL). The CD40 antigen is expressed predominantly on B-cells and represents a potential target for immune-based therapies. SGN-40 is a humanized IgG1 monoclonal antibody currently in Phase I/II clinical trials for indolent lymphomas, diffuse large B cell lymphomas and Multiple Myeloma. Its biological effect on CLL cells has not been studied. The present study demonstrated that SGN-40 mediated modest apoptosis in a subset of patients with secondary cross-linking but did not mediate complementdependent cytotoxicity. SGN-40 also mediated antibody-dependent cellular cytotoxicity (ADCC) predominantly through natural killer (NK) cells. Previous studies by our group and others have demonstrated that lenalidomide upregulates CD40 expression on primary B CLL cells and activates NK-cells. We therefore examined for the combinatorial effect of lenalidomide and SGN-40 and demonstrated that both enhanced direct apoptosis and ADCC against primary CLL B cells. These data together provide justification for clinical trials of SGN-40 and lenalidomide in combination for CLL therapy.

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Expression of CD28 and CD40 in human myeloma cells: a comparative study with normal plasma cells

Cited by 41 publications

References 0 publications

Adenovirus transduction to effect CD40 signalling improves the immune stimulatory activity of myeloma cells

Adenovirus transduction to effect CD40 signalling improves the immune stimulatory activity of myeloma cells

Normal and clonal B lineage cells can be distinguished by their differential expression of B cell antigens and adhesion molecules in peripheral blood from multiple myeloma (MM) patients—diagnostic and clinical implications

The humanized CD40 antibody SGN‐40 demonstrates pre‐clinical activity that is enhanced by lenalidomide in chronic lymphocytic leukaemia

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