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Synergistic Activation of Innate and Adaptive Immune Mechanisms in the Treatment of Gonadotropin-Sensitive Tumors

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...

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Autores principales: Bose, Anjali, Huhtaniemi, Ilpo, Singh, Om, Pal, Rahul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3620410/
https://www.ncbi.nlm.nih.gov/pubmed/23593454
http://dx.doi.org/10.1371/journal.pone.0061288
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author Bose, Anjali
Huhtaniemi, Ilpo
Singh, Om
Pal, Rahul
author_facet Bose, Anjali
Huhtaniemi, Ilpo
Singh, Om
Pal, Rahul
author_sort Bose, Anjali
collection PubMed
description 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.
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spelling pubmed-36204102013-04-16 Synergistic Activation of Innate and Adaptive Immune Mechanisms in the Treatment of Gonadotropin-Sensitive Tumors Bose, Anjali Huhtaniemi, Ilpo Singh, Om Pal, Rahul PLoS One Research Article 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. Public Library of Science 2013-04-08 /pmc/articles/PMC3620410/ /pubmed/23593454 http://dx.doi.org/10.1371/journal.pone.0061288 Text en © 2013 Bose et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bose, Anjali
Huhtaniemi, Ilpo
Singh, Om
Pal, Rahul
Synergistic Activation of Innate and Adaptive Immune Mechanisms in the Treatment of Gonadotropin-Sensitive Tumors
title Synergistic Activation of Innate and Adaptive Immune Mechanisms in the Treatment of Gonadotropin-Sensitive Tumors
title_full Synergistic Activation of Innate and Adaptive Immune Mechanisms in the Treatment of Gonadotropin-Sensitive Tumors
title_fullStr Synergistic Activation of Innate and Adaptive Immune Mechanisms in the Treatment of Gonadotropin-Sensitive Tumors
title_full_unstemmed Synergistic Activation of Innate and Adaptive Immune Mechanisms in the Treatment of Gonadotropin-Sensitive Tumors
title_short Synergistic Activation of Innate and Adaptive Immune Mechanisms in the Treatment of Gonadotropin-Sensitive Tumors
title_sort synergistic activation of innate and adaptive immune mechanisms in the treatment of gonadotropin-sensitive tumors
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3620410/
https://www.ncbi.nlm.nih.gov/pubmed/23593454
http://dx.doi.org/10.1371/journal.pone.0061288
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