Sperm protein 17 (Sp17) is a suitable target for immunotherapy of multiple myeloma

Chiriva‐Internati, Maurizio; Wang, Zhiqing; Salati, Emanuela; Bumm, Klaus; Barlogie, Bart; Lim, Seah H.

doi:10.1182/blood-2002-02-0408

Cited by 90 publications

(78 citation statements)

References 20 publications

(19 reference statements)

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“…Another category, the cancer-testis (CT) Ags, is expressed by testis cells and malignant cells mainly from patients with melanoma, small cell lung cancer, hepatocellular carcinoma, or bladder cancer (18). To date, 47 CT gene families that include 93 genes have been described (19 -22). Strictly testis-restricted genes that are expressed only by male germ cells and malignant cells, represent about one-half of CT genes (19).…”

Section: Ultiple Myeloma (Mm) 3 Is a B Cell Neoplasia Charac-mentioning

confidence: 99%

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

Condomines

Hose

Raynaud

et al. 2007

The Journal of Immunology

108

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Cancer-testis (CT) Ags are expressed in testis and malignant tumors but rarely in nongametogenic tissues. Due to this pattern, they represent attractive targets for cancer vaccination approaches. The aims of the present study are: 1) to assess the expression of CT genes on a pangenomic base in multiple myeloma (MM); 2) to assess the prognosis value of CT gene expression; and 3) to provide selection strategies for CT Ags in clinical vaccination trials. We report the expression pattern of CT genes in purified MM cells (MMC) of 64 patients with newly diagnosed MM and12 patients with monoclonal gammopathy of unknown significance, in normal plasma cell and B cell samples, and in 20 MMC lines. Of the 46 CT genes interrogated by the Affymetrix HG-U133 set arrays, 35 are expressed in the MMC of at least one patient. Of these, 25 are located on chromosome X. The expression of six CT genes is associated with a shorter event-free survival. The MMC of 98% of the patients express at least one CT gene, 86% at least two, and 70% at least three CT genes. By using a set of 10 CT genes including KM-HN-1, MAGE-C1, MAGE-A3/6/12, MAGE-A5, MORC, DDX43, SPACA3, SSX-4, GAGE-1–8, and MAGE-C2, a combination of at least three CT genes—desirable for circumventing tumor escape mechanisms—is obtained in the MMC of 67% of the patients. Provided that the immunogenicity of the products of these 10 CT genes is confirmed, gene expression profiling could be useful in identifying which CT Ags could be used to vaccinate a given patient.

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Section: Ultiple Myeloma (Mm) 3 Is a B Cell Neoplasia Charac-mentioning

confidence: 99%

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

Condomines

Hose

Raynaud

et al. 2007

The Journal of Immunology

108

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“…15,57 In addition, sperm protein 17 (Sp17) was described as a suitable target for the immunotherapy of MM with antigen-specific cytotoxic T cells, but was not yet evaluated for an antibodybased immunotherapeutic approach. 58 In contrast, in our experiments with the bscWue-1 Â CD3 Ab using primary myeloma cells and autologous T cells, an E:T ratio of 1:2 was sufficient for myeloma cell lysis. Another possible advantage of the single-chain antibody construct presented compared to other plasma-cell-associated antibodies described, so far, may be its low molecular weight that might improve its penetration into malignant tissue, as has been shown for Fab or Fv antibody fragments.…”

Section: Discussionmentioning

confidence: 45%

A novel recombinant bispecific single-chain antibody, bscWue-1 × CD3, induces T-cell-mediated cytotoxicity towards human multiple myeloma cells

Hönemann

Kufer²,

Rimpler

et al. 2004

Leukemia

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The development of antibody-based strategies for the treatment of multiple myeloma (MM) has been hampered so far by the fact that suitable plasma cell-specific surface antigens have been missing. However, recently a novel monoclonal antibody, designated Wue-1, has been generated that specifically recognizes normal and malignant human plasma cells. Therefore, Wue-1 is an interesting and promising candidate to develop novel immunotherapeutic strategies for the treatment of MM. One variant for an antibody-based strategy is the bispecific antibody approach. Recombinant bispecific single-chain (bsc) antibodies are especially interesting candidates because they show exceptional biological properties. We have generated a novel MM-directed recombinant bsc antibody, bscWue-1 Â CD3, and analyzed the biological properties of this antibody using the MM cell line NCI-H929 and primary cells from the bone marrow of patients with MM. We were able to show that bscWue-1 Â CD3 induces efficient and selective T-cell-mediated cell death of NCI-H929 cells and primary myeloma cells in nine out of 11 cases. The bscWue-1 Â CD3 Ab is efficacious even at low E:T ratios, and with or without additional T-cell pre-or costimulation. Target cell lyses were specific for Wue-1 antigen-positive cells and could be blocked by the Wue-1 monoclonal antibody.

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“…Sperm protein 17 (Sp17), the other immunogenic TAA, has been used as a tumor antigen to load into DCs. Sp17-specific HLA class I-restricted CTLs were successfully generated by DCs that have been loaded with a recombinant Sp17 protein and the CTLs were able to kill autologous tumor cells that expressed Sp17 (Chiriva-Internati et al, 2002). The over-expression of hTERT on MM compared to normal cells indicated that this telomerase could be used as tumor antigen to induce antitumor immune responses (Vonderheide et al, 1999).…”

Section: Myeloma-associated Antigens-based DC Immunotherapymentioning

confidence: 97%

Cellular Immunotherapy Using Dendritic Cells Against Multiple Myeloma

Lee¹,

Lee²,

Nguyen-Pham³

2012

Multiple Myeloma - An Overview

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Sperm protein 17 (Sp17) is a suitable target for immunotherapy of multiple myeloma

Cited by 90 publications

References 20 publications

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

A novel recombinant bispecific single-chain antibody, bscWue-1 × CD3, induces T-cell-mediated cytotoxicity towards human multiple myeloma cells

Cellular Immunotherapy Using Dendritic Cells Against Multiple Myeloma

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