Maternal immunization is successfully applied against some life-threatening infectious diseases as it can protect the mother and her offspring through the passive transfer of maternal antibodies. Here, we sought to evaluate whether the concept of maternal immunization could also be applied to cancer immune-prevention. We have previously shown that antibodies induced by DNA vaccination against rat Her2 (neu) protect heterozygous neu-transgenic female (BALB-neuT) mice from autochthonous mammary tumor development. We, herein, seek to evaluate whether a similar maternal immunization can confer antitumor protection to BALB-neuT offspring. Significantly extended tumor-free survival was observed in BALB-neuT offspring born and fed by mothers vaccinated against neu, as compared to controls. Maternally derived anti-neu immunoglobulin G (IgG) was successfully transferred from mothers to newborns and was responsible for the protective effect. Vaccinated mothers and offspring also developed active immunity against neu as revealed by the presence of T-cell-mediated cytotoxicity against the neu immunodominant peptide. This active response was due to the milk transfer of immune complexes that were formed between the neu extracellular domain, shed from vaccine-transfected muscle cells, and the anti-neu IgG induced by the vaccine. These findings show that maternal immunization has the potential to hamper mammary cancer in genetically predestinated offspring and to develop into applications against lethal neonatal cancer diseases for which therapeutic options are currently unavailable.

Antitumor immunization of mothers delays tumor development in cancer-prone offspring

BARUTELLO, GIUSEPPINA;CURCIO, CLAUDIA;SPADARO, Michela;ARIGONI, MADDALENA;BOLLI, ELISABETTA;QUAGLINO, Elena;RICCARDO, FEDERICA;FORNI, Guido;CAVALLO, Federica
2015

Abstract

Maternal immunization is successfully applied against some life-threatening infectious diseases as it can protect the mother and her offspring through the passive transfer of maternal antibodies. Here, we sought to evaluate whether the concept of maternal immunization could also be applied to cancer immune-prevention. We have previously shown that antibodies induced by DNA vaccination against rat Her2 (neu) protect heterozygous neu-transgenic female (BALB-neuT) mice from autochthonous mammary tumor development. We, herein, seek to evaluate whether a similar maternal immunization can confer antitumor protection to BALB-neuT offspring. Significantly extended tumor-free survival was observed in BALB-neuT offspring born and fed by mothers vaccinated against neu, as compared to controls. Maternally derived anti-neu immunoglobulin G (IgG) was successfully transferred from mothers to newborns and was responsible for the protective effect. Vaccinated mothers and offspring also developed active immunity against neu as revealed by the presence of T-cell-mediated cytotoxicity against the neu immunodominant peptide. This active response was due to the milk transfer of immune complexes that were formed between the neu extracellular domain, shed from vaccine-transfected muscle cells, and the anti-neu IgG induced by the vaccine. These findings show that maternal immunization has the potential to hamper mammary cancer in genetically predestinated offspring and to develop into applications against lethal neonatal cancer diseases for which therapeutic options are currently unavailable.
ONCOIMMUNOLOGY
4
5
e1005500-1
e1005500-9
Amot; Angiomotin p80; BALB-neuT mice; BALB/c female mice KO for the μIg chain; ECTM; BALB/c mice KO for the Fc-gamma I/III receptors; FcγRI/III; BALB/c mice heterozygous for the transforming form of the neu transgene; BKO mice; DNA vaccination; Fc-gamma I/III receptors; IFNγ; Her2/neu; T-regulatory cell; antitumor vaccine; cancer immune-prevention; extracellular and transmembrane; FcγKO mice; interferon gamma; KO; knockout; LNs; lymph nodes; RSI; mammary cancer; maternal immunization; rate of stimulation index; SFU; splenocytes; Treg; spot-forming unit; SPC
Barutello, Giuseppina; Curcio, Claudia; Spadaro, Michela; Arigoni, Maddalena; Trovato, Rosalinda; Bolli, Elisabetta; Zheng, Yujuan; Ria, Francesco; Quaglino, Elena; Iezzi, Manuela; Riccardo, Federica; Holmgren, Lars; Forni, Guido; Cavallo, Federica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1542206
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