title: Synergistic activation of innate and adaptive immune mechanisms in the treatment of gonadotropin-sensitive tumors.
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/J(βhCG/-) 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.
authors.affiliation: Immunoendocrinology Lab, National Institute of Immunology, New Delhi, India.
authors.forename: Anjali
authors.initials: A
authors.lastname: Bose
authors.forename: Ilpo
authors.initials: I
authors.lastname: Huhtaniemi
authors.forename: Om
authors.initials: O
authors.lastname: Singh
authors.forename: Rahul
authors.initials: R
authors.lastname: Pal
mesh_terms: D056704:Adaptive Immunity; D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000382:microbiology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006063:Chorionic Gonadotropin / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007114:Immunization; D056747:Immunomodulation; D008297:Male; D051379:Mice; D009161:Mycobacterium / Q000502:physiology
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D006063:Chorionic Gonadotropin