Immunogenicity study of recombinant human sperm-associated antigen 9 in bonnet macaque (Macaca radiata)

Rana, Ritu; Jagadish, Nirmala; Garg, Manoj; Mishra, Deepshikha; Dahiya, Neetu; Chaurasiya, Dipak; Suri, Anil

doi:10.1093/humrep/del068

Cited by 7 publications

(4 citation statements)

References 26 publications

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“…Recently, we have shown that SPAG9 is highly immunogenic in vivo in EOC patients (8). In addition, our earlier immunogenicity studies in rodents and nonhuman primate showed the generation of antibodies against SPAG9 (26,27). In this context, it is relevant to mention here that a similar humoral response against SPAG9 was observed in the sera of RCC patients with 77% sample exhibiting circulating anti-SPAG9 antibody, suggesting its strong immunogenicity.…”

Section: Discussionmentioning

confidence: 50%

Sperm-Associated Antigen 9 Is Associated With Tumor Growth, Migration, and Invasion in Renal Cell Carcinoma

et al. 2008

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Renal cell carcinoma (RCC) represents one of the most resistant tumors to radiation and chemotherapy. Current therapies for RCC patients are inefficient due to the lack of diagnostic and therapeutic markers. Our recent studies have suggested an association of sperm-associated antigen 9 (SPAG9) with ovarian carcinomas. In the present study, we investigated the clinical relevance of SPAG9 in RCC patients. RT-PCR analysis showed expression of SPAG9 transcript in RCC tissues and RCC cell lines. In situ RNA hybridization and immunohistochemistry analyses confirmed the expression of SPAG9 in 88% of cancer patients, suggesting that SPAG9 participates in renal cancer. In addition, immunoblotting and ELISA analyses revealed a humoral immune response against SPAG9 in the sera of RCC patients but not in healthy individuals. Consistent with the clinical findings, knockdown of SPAG9 expression in RCC cells with specific siRNA significantly reduced cell growth and colony formation. Using in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also significantly inhibited. Furthermore, in vivo xenograft studies in nude mice revealed that administration of a SPAG9 siRNA plasmid significantly inhibited tumor growth. In conclusion, SPAG9 expression is associated with clinicopathologic features of tumors, suggesting that SPAG9 could contribute to the early spread of cancer. These results indicate that SPAG9 may have a role in tumor development and metastasis and thus could serve as a novel target for early detection and treatment of RCC. [Cancer Res 2008;68(20):8240-8]

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Section: Discussionmentioning

confidence: 50%

Sperm-Associated Antigen 9 Is Associated With Tumor Growth, Migration, and Invasion in Renal Cell Carcinoma

et al. 2008

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“…Subsequently, SPAG9 DNA immunization studies in mice also showed specific immune response against SPAG9 (16). Recently, the immunogenic potential of recombinant SPAG9 protein was evaluated in nonhuman primate model (25) for its eventual implications in the development of human contraceptive vaccine. This is particularly relevant that similar humoral response against SPAG9 was observed in EOC patients.…”

Section: Discussionmentioning

confidence: 99%

Sperm-Associated Antigen 9, a Novel Cancer Testis Antigen, Is a Potential Target for Immunotherapy in Epithelial Ovarian Cancer

Garg

Chaurasiya

Rana

et al. 2007

Clinical Cancer Research

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Purpose: Cancer testis antigens are a group of tumor antigens with gene expression restricted to male germ cells in the testis and in various cancerous tissues. Recently, we reported a novel testisspecific sperm-associated antigen 9 (SPAG9) gene, a new member of the c-Jun NH 2 -terminal kinase^interacting protein family, having functional role in sperm-egg fusion and mitogenactivated protein kinase signaling pathway. National Center for Biotechnology Information Blast searches revealed SPAG9 nucleotide sequence similarities with expressed sequence tags of various cancerous tissues. In an effort to examine the clinical utility of SPAG9, we investigated the SPAG9 mRNA and protein expression in epithelial ovarian cancer (EOC). Humoral immune response to SPAG9 was also evaluated in EOC patients. Experimental Design: We determined the expression profile of SPAG9 transcript by reverse transcription-PCR and RNA in situ hybridization and SPAG9 protein expression by immunohistochemistry in EOC specimens and human ovarian cancer cell lines. Using ELISA and Western blotting, we analyzed specific antibodies for SPAG9 in sera from patients with EOC. Results: SPAG9 mRNA and protein expression was detected in 90% of EOC tissues and in all three human ovarian cancer cell lines. Specific SPAG9 antibodies were detected in 67% of EOC patients and not in sera from healthy individuals. Conclusions: Our findings indicate that SPAG9 is highly expressed in EOC and immunogenic in patients. Humoral immune response against SPAG9 in early stages of EOC suggests its important role in early diagnostics.These results collectively suggest that SPAG9, a novel member of cancer testis antigen family, could be a potential target for the development of diagnostic and therapeutic methods in EOC.

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“…It also indicated higher level of antibodies against the respective antigens in the blood serum of dogs 1 -8 during this period. In the similar studies in Macaca radiata, Rana et al [28] also observed an elevated antibody titre after the first booster which was significantly higher from week 8 -12 against human sperm associated antigen 9. Immunization of bulls against spermatozoa resulted in transient rise in the level of IgM antibodies and persistent elevated levels of IgG1 and IgG2 in the serum [29].…”

Section: Immune Response To Ph-20 and Ldhc Sub Unitsmentioning

confidence: 67%

Immuno-contraceptive potential of sperm specific LDHC4 and SPAM-1 (PH-20) sub units in dog

Cheema¹,

Vashishat²,

Bansal³

et al. 2012

OJAS

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PH-20 (Spam-1) antigen appears to be a bi-functional sperm plasma membrane protein with hyaluronidase activity and its role is related to cumulus penetration as well as zona binding. (LDH-C4) is a key enzyme, distributed specifically in testis and is highly immunogenic, function of which relates to energy metabolism and capacitation of the sperm. Therefore, in this study, we observed the effect of purified native PH-20 and LDH-C4 antigens on sperm function and morphology in dog. Native PH-20 (46, 32 kDa) and LDH-C4 (36, 30, 28) sub units, purified from dog sperm SDS- extracts were used to test as immunocontraceptive candidates in stray dog. Dogs 1, 2, 3, 4, 5/6 and 7/8 were immunized with 46, 32, 36, 30/28, 46/32, 36/30/28 kDa sub units respectively by i/m route and semen was analysed at weekly intervals. High titre of 3200 - 6400 was achieved in all dogs after three boosters. Immune response in treated dogs was confirmed by increase in Ig level in blood serum and reaction of partially purified serum Ig of immunized dogs with respective antigens in double immune diffusion and immunoblots. Immunization of dogs either with individual PH-20/ LDHC sub units or pooled PH-20/LDHC4 sub units showed a significant effect on sperm count, percent motility, viability, HOST and sperm morphology. All the sperm parameters declined to a significant level (p < 0.05) between 45 - 115 DPI and remained low than that of the recommended values for fertile dog semen till 175 DPI. The incubation of spermatozoa in HOS solution in the presence of anti-PH-20 and anti-LDHC Ig significantly reduced the percent HOS positive spermatozoa. A significant decline (p ≤ 0.05) in acrylamide penetration assay was also observed in the presence of anti 46 and 30/28 kDa Ig. Since percent motility, sperm count, HOST and percent normal spermatozoa in immunized dogs were significantly less than that of recommended fertile dog semen, it can be concluded that PH-20 (46/32 kDa) and LDHC4 (36/30/28 kDa) sub units had an immunocontraceptive potential in dog

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Immunogenicity study of recombinant human sperm-associated antigen 9 in bonnet macaque (Macaca radiata)

Abstract: These results demonstrate that rhSPAG9 adsorbed on alum is highly immunogenic in subhuman primate model and therefore represents a suitable sperm-based vaccine immunogen for fertility trials in macaque.

Cited by 7 publications

References 26 publications

Sperm-Associated Antigen 9 Is Associated With Tumor Growth, Migration, and Invasion in Renal Cell Carcinoma

Sperm-Associated Antigen 9 Is Associated With Tumor Growth, Migration, and Invasion in Renal Cell Carcinoma

Sperm-Associated Antigen 9, a Novel Cancer Testis Antigen, Is a Potential Target for Immunotherapy in Epithelial Ovarian Cancer

Immuno-contraceptive potential of sperm specific LDHC<sub>4</sub> and SPAM-1 (PH-20) sub units in dog

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Immunogenicity study of recombinant human sperm-associated antigen 9 in bonnet macaque (Macaca radiata)

Abstract: These results demonstrate that rhSPAG9 adsorbed on alum is highly immunogenic in subhuman primate model and therefore represents a suitable sperm-based vaccine immunogen for fertility trials in macaque.

Cited by 7 publications

References 26 publications

Sperm-Associated Antigen 9 Is Associated With Tumor Growth, Migration, and Invasion in Renal Cell Carcinoma

Sperm-Associated Antigen 9 Is Associated With Tumor Growth, Migration, and Invasion in Renal Cell Carcinoma

Sperm-Associated Antigen 9, a Novel Cancer Testis Antigen, Is a Potential Target for Immunotherapy in Epithelial Ovarian Cancer

Immuno-contraceptive potential of sperm specific LDHC&lt;sub&gt;4&lt;/sub&gt; and SPAM-1 (PH-20) sub units in dog

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Immuno-contraceptive potential of sperm specific LDHC<sub>4</sub> and SPAM-1 (PH-20) sub units in dog