Sperm protein 17 is a novel cancer-testis antigen in multiple myeloma

Lim, Seah H.; Wang, Zhiqing; Chiriva‐Internati, Maurizio; Xue, Yuying

doi:10.1182/blood.v97.5.1508

Cited by 122 publications

(102 citation statements)

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“…3 Briefly, total RNA was extracted from ovarian tumor cells using the Tri-reagent (Sigma Chemical Company, St. Louis, MO). All RNA specimens first were treated with DNAse I (Ambion, Inc., Austin, TX) to remove genomic DNA contamination.…”

Section: Reverse Transcriptase-polymerase Chain Reaction Detection Ofmentioning

confidence: 99%

Tumor vaccine for ovarian carcinoma targeting sperm protein 17

Chiriva‐Internati

Wang

Salati

et al. 2002

Cancer

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BACKGROUNDThe authors previously identified sperm protein 17 (Sp17) as being expressed in patients with multiple myeloma. The restricted expression of Sp17 in normal tissue makes it an ideal target for tumor vaccine. In the current study, the authors extended their research to include ovarian carcinoma.METHODSA pair of sequence specific primers was used in reverse transcriptase‐polymerase chain reaction to determine the gene expression of Sp17. A recombinant Sp17 protein was used with monocyte‐derived dendritic cells and autologous peripheral blood mononuclear cells to generate Sp17 specific cytotoxic T‐lymphocytes (CTLs). The successful generation of Sp17 specific CTLs was confirmed using standard 51chromium‐release assays.RESULTSSp17 was found to be expressed in the primary tumor cells from 70% of the patients with ovarian carcinoma. Human leukocyte antigen (HLA) class I‐ restricted Sp17 specific CTLs were generated successfully from the peripheral blood of three patients with ovarian carcinoma at the time of disease presentation. These CTLs were able to lyse autologous Epstein‐Barr virus‐transformed lymphoblastoid cells in a Sp17‐dependent manner. Target lysis was HLA class I‐dependent and could be blocked by antibodies against monomorphic HLA class I but not HLA class II molecules. The CTLs also lysed Sp17‐positive autologous tumor cells, suggesting that Sp17 is processed and presented in association with the HLA class I molecules in Sp17‐ positive tumor cells in a concentration and configuration that could be recognized by recombinant protein‐primed CTLs. Tumor cell killing by the CTLs appeared to be mediated through the perforin pathway. Flow cytometric analysis of the CTLs indicated that they predominantly were CD8 in phenotype and produced interferon‐γ and scant amounts of interleukin‐4.CONCLUSIONSThe results of the current study suggest the potential of Sp17 as a target for immunotherapy in patients with ovarian carcinoma. Cancer 2002;94:2447–53. © 2002 American Cancer Society.DOI 10.1002/cncr.10506

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Section: Reverse Transcriptase-polymerase Chain Reaction Detection Ofmentioning

confidence: 99%

Tumor vaccine for ovarian carcinoma targeting sperm protein 17

Chiriva‐Internati

Wang

Salati

et al. 2002

Cancer

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“…6,7 Although Sp17 has been frequently reported to be expressed solely in the testis, transcripts have recently been detected in murine somatic tissues by RT-PCR, albeit in much lower amounts when compared to testis. 8 Despite Lim et al 4 having failed to detect mRNA encoding HSp17 in human somatic tissues other than the testis, Frayne and Hall 9 have clearly detected HSp17 transcripts of the predicted size in a panel of human cDNAs including the brain, heart, kidney, liver, lung, pancreas, placenta and testis.In clinical materials, the expression of CT antigens has mostly been studied at the level of gene expression by RT-PCR. However the information provided by this approach is limited because of the impossibility of quantifying cancer cells that are positive for CT antigens.…”

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confidence: 99%

Some remarks on the somatic expression of sperm protein 17

Grizzi

Franceschini

Hermonat³

et al. 2004

Intl Journal of Cancer

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Dear Sir,We read with interest the article by Straughn et al.,"Expression of sperm protein 17 (Sp17) in ovarian cancer". 1 Although this study is a significant contribution to the field of cancer research, the following observations need to be made.Sperm protein 17 (Sp17) is a highly conserved mammalian protein detected in mouse, monkey, baboon, macaque and human (HSp17) testis and spermatozoa. Using a pair of sequence-specific primers, the presence of HSp17 mRNA has been clearly shown in 17% of patients with multiple myeloma and in the primary tumor cells from 70% of patients with ovarian carcinoma. 2-4 Chiriva-Internati et al. 5 have further shown that HSp17 contains functional cytotoxic T-lymphocyte epitopes. These results indicate that HSp17 is a cancer-testis (CT) antigen in multiple myeloma and ovarian carcinoma and suggest its suitability as a target for immunotherapy of these 2 neoplastic diseases.CT antigens constitute a group of proteins expressed in histologically different types of neoplasia and whose expression in normal tissues is limited to germ cells of the testis, with occasional expression in female reproductive organs. 6,7 Although Sp17 has been frequently reported to be expressed solely in the testis, transcripts have recently been detected in murine somatic tissues by RT-PCR, albeit in much lower amounts when compared to testis. 8 Despite Lim et al. 4 having failed to detect mRNA encoding HSp17 in human somatic tissues other than the testis, Frayne and Hall 9 have clearly detected HSp17 transcripts of the predicted size in a panel of human cDNAs including the brain, heart, kidney, liver, lung, pancreas, placenta and testis.In clinical materials, the expression of CT antigens has mostly been studied at the level of gene expression by RT-PCR. However the information provided by this approach is limited because of the impossibility of quantifying cancer cells that are positive for CT antigens. 7,10 On the contrary, by means of specific antibodies it is possible to recognize the presence of the antigen within examined tissues, highlighting not only the quantity but also the type of cells immunopositive for that antigen.By using self-produced mouse anti-HSp17 antibodies, normal human seminiferous tubules were highly positive for HSp17 as well as the flagella of the ejaculated spermatozoa. 11 Since the flagella of spermatozoa are similar to cilia, we then investigated whether HSp17 was identifiable in human ciliated epithelia. We detected a strong presence of HSp17 in ciliated epithelia of the respiratory airways and both the male and female reproductive system. 12 These data extend recent reports in which a proteomic analysis of human airways cilia revealed the expression of HSp17 13 and in which a RT-PCR analysis from a panel of human cDNAs showed HSp17 transcripts in all human tissues examined, including lung and other organs that contain different amounts of ciliated cells. 9 Since cilia have been adapted as versatile tools for many biological processes, such as left-right axis pattern formati...

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“…Using a bioinformatics approach, we have identified Sp17 expressed, both at mRNA and protein levels, in fresh human tumor cells derived from multiple myeloma (MM) [25] and ovarian cancer (OC) [27]. The aberrant expression of Sp17 in tumor cells is regulated through promoter methylation [28].…”

Section: Sperm Protein 17 (Sp17) As a New Member Of Ct Antigensmentioning

confidence: 99%

Cancer immunotherapy targeting Sp17: When should the laboratory findings be translated to the clinics?

et al. 2005

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Despite advances in chemotherapeutic agents, the prognosis for some cancers remains extremely poor, suggesting the need for other treatment modalities. Immunotherapy appears an ideal approach because the mechanisms of tumor cell killing induced by tumor vaccines are different from those from chemotherapy. Various investigations are ongoing to identify suitable targets for this purpose. Sperm protein 17 (Sp17) was originally identified by our group as a novel cancer-testis antigen in various malignancies, including multiple myeloma. Sp17 is a highly immunogenic protein and the observation that more than 90% of vasectomized males develop immunity against Sp17 suggests the opportunity and safety of Sp17 for tumor vaccines. Recent works by other workers suggest a low level of expression of Sp17 in some normal tissues, and investigators have questioned whether Sp17 is in fact a suitable target for immunotherapy. In this paper, we review the general principles of immunotherapy and provide evidence supporting the highly immunogenic nature of Sp17. We also address the discrepancies between the objectives of oncologists involved in treating cancer patients and their familiarity with acceptable levels of toxicity of any effective therapy and those of pure laboratory-based investigators. Finally, we present some early clinical data supporting the rationale for further investigations of Sp17 for tumor vaccines. Am.

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Sperm protein 17 is a novel cancer-testis antigen in multiple myeloma

Cited by 122 publications

References 12 publications

Tumor vaccine for ovarian carcinoma targeting sperm protein 17

Tumor vaccine for ovarian carcinoma targeting sperm protein 17

Some remarks on the somatic expression of sperm protein 17

Cancer immunotherapy targeting Sp17: When should the laboratory findings be translated to the clinics?

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