| First Author | Bose A | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 4 | Pages | e61288 |
| PubMed ID | 23593454 | Mgi Jnum | J:200025 |
| Mgi Id | MGI:5506838 | Doi | 10.1371/journal.pone.0061288 |
| Citation | Bose A, et al. (2013) Synergistic activation of innate and adaptive immune mechanisms in the treatment of gonadotropin-sensitive tumors. PLoS One 8(4):e61288 |
| abstractText | 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/J(betahCG/-) 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 IFNgamma, IL-6, IL-12p40, KC and TNFalpha from murine antigen presenting cells. When MIP was incorporated into an anti-hCG vaccine formulation previously employed in humans (a betahCG-TT conjugate adsorbed on alum), elevated T cell recall proliferative and cytokine responses to hCG, betahCG 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 betahCG-TT to BALB/c mice subcutaneously implanted with SP2/O cells resulted in anti-tumor effects; significantly, immunization with betahCG-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. |
