Abstract
Human chorionic gonadotropin (hCG) prolongs the secretion of progesterone from the corpus luteum, providing a critical stimulus for the sustenance of pregnancy. hCG (or individual subunits) is also secreted by a variety of trophoblastic and non-trophoblastic cancers and has been associated with poor prognosis. Early clinical studies have indicated merit in anti-hCG vaccination as potential immunotherapy, but anti-tumor efficacy is believed to be compromised by sub-optimal immunogenecity. In the present study, enhanced tumorigenesis was observed when SP2/O cells were subcutaneously injected in either male or female BALB/c x FVB/JβhCG/- F1 transgenic mice, establishing the growth-promoting effects of the gonadotropin for implanted tumors in vivo. The utility of Mycobacterium indicus pranii (MIP) was evaluated, as an innate anti-tumor immunomodulator as well as adjuvant in mice. MIP elicited the secretion of the inflammatory cytokines IFNγ, IL-6, IL-12p40, KC and TNFα from murine antigen presenting cells. When MIP was incorporated into an anti-hCG vaccine formulation previously employed in humans (a βhCG-TT conjugate adsorbed on alum), elevated T cell recall proliferative and cytokine responses to hCG, βhCG and TT were observed. MIP increased vaccine immunogenicity in mice of diverse genetic background (including in traditionally low-responder murine strains), leading to enhanced titres of bioneutralizing anti-hCG antibodies which exhibited cytotoxicity towards tumor cells. Individual administration of MIP and βhCG-TT to BALB/c mice subcutaneously implanted with SP2/O cells resulted in anti-tumor effects; significantly, immunization with βhCG-TT supplemented with MIP invoked synergistic benefits in terms of tumor volume, incidence and survival. The development of novel vaccine formulations stimulating both adaptive and innate anti-tumor immunity to induce collaborative beneficial effects may fill a niche in the adjunct treatment of hCG-sensitive tumors that are resistant to conventional therapy.
Highlights
Human chorionic gonadotropin, a heterodimeric glycoprotein hormone, is considered crucial for the establishment of pregnancy
The unexpected association of Human chorionic gonadotropin (hCG) with tumorigenesis [1] as well as its link to poor patient survival outcomes [2,3] have sparked interest in strategies that target the molecule for the control of malignancy
A vaccine based on the C-terminal peptide (CTP) of bhCG has undergone Phase II trials in patients of metastatic colorectal cancer; anti-hCG antibody induction was shown to be associated with improved survival [12]
Summary
Human chorionic gonadotropin (hCG), a heterodimeric glycoprotein hormone, is considered crucial for the establishment of pregnancy. Earlier efficacy studies with vaccines targeting the bhCG subunit (employed either as a contraceptive measure in women [9] or as immunotherapy in patients of colorectal cancer [12]) provided proof of safety and efficacy It was surmised, that more immunogenic formulations could result in enhanced benefit. Using heterozygous male and female bhCG transgenic mice, this study unequivocally established the growth-promoting effects of bhCG/hCG on implanted, histocompatible tumor cells It further describes the benefits of MIP as a supplemental additive to an antihCG vaccine formulation previously tested in humans, both as an adjuvant for the enhanced generation of anti-hCG immune responses, as well as an elicitor of independent innate anti-tumor immunity. Results revealed that MIP can have a variety of immunomodulatory effects, and co-administration along with active antihCG immunization can result in substantial reductions in tumor incidence and volume, as well as enhancement in life-span
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
