Talwar Research Foundation, E-8 Neb Valley, New Delhi, India.
J Reprod Immunol. 2009 Dec;83(1-2):158-63. doi: 10.1016/j.jri.2009.08.008. Epub 2009 Oct 24.
Gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) are unique targets for the control of fertility. Immunological approaches to neutralizing these hormones have additional utility in cancer treatment. Vaccines have been developed against both GnRH and hCG and these have undergone Phase I/II clinical trials documenting their safety, reversibility and efficacy. The heterospecies dimer hCG vaccine prevented pregnancy in women of proven fertility without impairment of ovulation or derangement of menstrual regularity and bleeding profiles. The protective threshold of antibody titers to achieve efficacy was determined in these first-ever trials. Recently, a recombinant vaccine against the beta subunit of hCG linked to the B subunit of heat labile enterotoxin has been made and expressed as a glycosylated conjugate in Pichia pastoris. Experiments indicate its ability to generate antibodies above the protective threshold in all immunized Balb/c mice. Ectopic expression of hCG/hCGbeta is observed in many advanced stage cancers of various origins. A chimeric high affinity and specific recombinant antibody against hCGbeta linked to curcumin kills hCGbeta expressing T lymphoblastic leukemia cells without any deleterious effect. Several synthetic and recombinant vaccines have been developed against GnRH. These reduce serum testosterone to castration levels causing atrophy of the prostate. Three Phase I/II clinical trials conducted in India and Austria have shown that these vaccines elicit non-surgical reduction of testosterone, a fall in prostate specific antigen and clinical improvement of prostate carcinoma patients. A multimer recombinant vaccine against GnRH has high efficacy for sterilization of pigs and other animals.
促性腺激素释放激素（GnRH）和人绒毛膜促性腺激素（hCG）是控制生育能力的独特靶点。针对这些激素的免疫方法在癌症治疗中具有额外的应用。已经开发出针对 GnRH 和 hCG 的疫苗，这些疫苗已经进行了 I/II 期临床试验，证明了它们的安全性、可逆性和疗效。异源二聚体 hCG 疫苗在具有生育能力的女性中预防怀孕，而不影响排卵或扰乱月经规律和出血模式。在这些首次试验中确定了达到疗效的抗体滴度保护阈值。最近，已经开发出一种针对 hCG 的β亚单位与不耐热肠毒素 B 亚单位连接的重组疫苗，并在毕赤酵母中作为糖基化缀合物表达。实验表明，它能够在所有免疫的 Balb/c 小鼠中产生高于保护阈值的抗体。在许多起源不同的晚期癌症中都观察到 hCG/hCGβ的异位表达。一种针对 hCGβ的嵌合高亲和力和特异性重组抗体与姜黄素连接，可杀死表达 hCGβ的 T 淋巴细胞白血病细胞，而无任何不良影响。已经开发出几种针对 GnRH 的合成和重组疫苗。这些疫苗将血清睾酮降低至去势水平，导致前列腺萎缩。在印度和奥地利进行的三项 I/II 期临床试验表明，这些疫苗可引起非手术性睾酮降低、前列腺特异性抗原下降和前列腺癌患者的临床改善。针对 GnRH 的多聚体重组疫苗对猪和其他动物具有很高的绝育效果。
