We report here results of clinical trials on a birth control vaccine, consisting of a heterospecies dimer of the .3 subunit of human chorionic gonadotropin (hCG) associated noncovalently with the a subunit of ovine luteinizing hormone and coijugated to tetanus and diphtheria toxoids as carriers, that induces antibodies of high avidity (Ka 1010 M-) against hCG. Fertile women exposed to conception over 1224 cycles recorded only one pregnancy at antibody titers of >50 ng/ml (hCG bioneutralization capacity). The antibody response declines with time; fertility was regained when titers fell to <35 ng/ml. This study presents evidence of the feasibility of a vaccine for control of human fertility.A number of contraceptive methods are available; they do not, however, suit all potential users. There is need to develop additional methods, in particular those that are reversible, require only periodic intake, and do not disturb menstrual regularity or bleeding. Vaccines regulating fertility offer promising prospects to meet these specifications. The rationale for these vaccines is to induce the formation of antibodies and/or cell-mediated immunity to intercept selectively a process critical to the success of reproduction. A number of potential antigens are being investigated (1-7). Among these are hormones, which play an important role in the regulation of fertility. Human chorionic gonadotropin (hCG) is an early signal of conception and is considered essential for establishment and maintenance of early pregnancy. An advantage in choosing hCG as a target for immunocontraception is that its inactivation would not interfere with other physiological processes in the female, such as ovulation and production of sex steroid hormones.Carrier conjugation with tetanus toxoid (TT) was proposed as a strategy to overcome the immunological tolerance of a woman against hCG (8). This initial prototype vaccine (/3hCG-TT adsorbed on alum) had limitations. It induced high antibody titers in only a small percentage of women, and those with low titers were not protected from pregnancy (9). Three changes were made to enhance immunogenicity.(i) An adjuvant, the sodium phthalyl derivative of lipopolysaccharide, was included in the first injection. This nonpyrogenic adjuvant is usable in aqueous phase (10). Its use doubled, on average, anti-hCG titers and increased the frequency of high responders.(ii) The intrinsic immunogenicity of (3hCG was enhanced by associating it noncovalently with the a subunit of ovine luteinizing hormone (LH) to form a heterospecies dimer (HSD), a laboratory-made hormone that attains a conformation which recognizes receptors on target tissues (whereas isolated subunits do not) and generates a steroidogenic response even superior to that by hCG (11). HSD linked to carriers was indeed found to be more immunogenic than ,8hCG in rats and monkeys (12). Moreover, the antibodies had better capacity to neutralize the bioactivity of hCG (11,13 It was important to determine whether the antibodies induced by the HSD-and 8hC...

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.

BACKGROUND: Cervical cancer is a major cause of death among women worldwide, and the most cases are reported in the least developed countries. Recently, a study on DNA microarray gene expression analysis demonstrated the overexpression of heat shock protein 70-2 (HSP70-2) in cervical carcinoma cells (HeLa). The objective of the current study was to evaluate the association between HSP70-2 expression in cervical carcinogenesis and its potential role in various malignant properties that result in disease progression. METHODS: HSP70-2 expression was examined in various cervical cancer cell lines with different origins and in clinical cervical cancer specimens by reverse transcriptasepolymerase chain reaction (RT-PCR), flow cytometry, and immunohistochemistry (IHC) analyses. A plasmid-based, short-hairpin RNA approach was used specifically to knock down the expression of HSP70-2 in cervical tumor cells in vitro and in vivo to examine the role of HSP70-2 on various malignant properties. RESULTS: RT-PCR and IHC analyses revealed HSP70-2 expression in 86% of cervical cancer specimens. Furthermore, knockdown of HSP70-2 expression significantly reduced cellular growth, colony formation, migration, and invasion in vitro and reduced tumor growth in vivo. A significant association of HSP70-2 gene and protein expression was observed among the various tumor stages (P ¼ .046) and different grades (P ¼ .006), suggesting that HSP70-2 expression may be an indicator of disease progression. CONCLUSIONS: The current findings suggested that HSP70-2 may play an important role in disease progression in cervical carcinogenesis. Patients who had early stage disease and low-grade tumors had HSP70-2 expression, supporting its potential role in early detection and aggressive treatment modalities for cervical cancer management. Cancer 2010;116:3785-96.

BACKGROUND: Cervical cancer is the second most common malignancy in women, with nearly half a million new cases diagnosed each year worldwide. The authors' recent studies have suggested an association

SPAG9 expression may play a role in cellular growth and thyroid carcinogenesis. These findings support a potential role for SPAG9 as diagnostic biomarker as well as a possible therapeutic target in thyroid cancer treatment.