Tumor vaccine for ovarian carcinoma targeting sperm protein 17.
BACKGROUND
The 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.


METHODS
A 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 (51)chromium-release assays.


RESULTS
Sp17 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-gamma and scant amounts of interleukin-4.


CONCLUSIONS
The results of the current study suggest the potential of Sp17 as a target for immunotherapy in patients with ovarian carcinoma.
Chiriva-Internati
Maurizio
M
Division of Hematology and Oncology, Texas Tech University School of Medicine at Amarillo, USA.
Wang
Zhiqing
Z
Salati
Emanuela
E
Timmins
Patrick
P
Lim
Seah H
SH
D000954:Antigens, Surface; D002148:Calmodulin-Binding Proteins; D019496:Cancer Vaccines / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006680:HLA Antigens; D006801:Humans; D016130:Immunophenotyping; D008565:Membrane Proteins; D009101:Multiple Myeloma / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology; D010051:Ovarian Neoplasms / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000954:Antigens, Surface; D002148:Calmodulin-Binding Proteins; D019496:Cancer Vaccines; D002352:Carrier Proteins; D016207:Cytokines; D006680:HLA Antigens; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; C090172:SPA17 protein, human