Abstract 5860
Background
Neuroblastoma (NB) is the most common extracranial solid tumor in infancy. Some germline and somatic mutations associated with NB have been identified as activating mutations of the anaplastic lymphoma kinase (ALK) oncogene. Because of the nature of NB, which can occur in the early post-natal life or even during fetal life, we evaluated the efficacy of a DNA vaccine against ALK in a spontaneous preclinical model of NB, harboring ALKF1174L mutation in association with MYCN amplification (ALKF1174L/MYCN mice) by means of maternal immunization (MI).
Methods
MYCN transgenic females were immunized against ALK by DNA vaccination by using a plasmid coding for the extracellular and trans-membrane domains of human ALK (ALK-ECTM) followed by electroporation, and then they were mated with an ALKF1174L-transgenic male. In ALKF1174L/MYCN offspring, the presence of abdominal, cervical and paraspinal tumors has been evaluated and quantified by Magnetic Resonance Imaging. The humoral immune response induced against ALK in the mothers and their offspring, as well as the presence of immune-complexes containing ALK, have been evaluated by ELISA. ALK expression in tumor tissue was assessed by Western blot.
Results
Pre-birth immunization against ALK leads to an extended survival time and to a lower tumor growth kinetic in ALKF1174L/MYCN offspring born from ALK-ECTM-vaccinated mothers (ALK-ECTM offspring) as compared to controls born from control empty vector-vaccinated mothers. Maternally derived anti-ALK antibodies were successfully transferred from mothers to newborns. Moreover, anti-ALK IgM were found in the sera of five- and six-week old ALK-ECTM offspring, suggesting the induction of the pups’ own immune response against ALK. This effect could be due to the breast milk-mediated transfer of immune-complexes containing ALK, found in the milk of vaccinated mothers and in their offspring sera. Finally, MI against ALK induces a decrease in ALK expression in ALK-ECTM offspring’ tumor tissue.
Conclusions
Overall, these results indicate that MI against ALK induces an active immunization against this oncoantigen in the offspring, impairing tumor development and enhancing survival time in a preclinical model of NB.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Department of Molecular Biotechnology and Health Sciences.
Funding
Associazione Italiana per la ricerca sul Cancro.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5655 - Bioactivation of napabucasin triggers reactive oxygen species–mediated cancer cell death
Presenter: Fieke Froeling
Session: Poster Display session 3
Resources:
Abstract
4097 - Targeting NRG1-fusions in multiple tumour types: Afatinib as a novel potential treatment option
Presenter: Stephen V Liu
Session: Poster Display session 3
Resources:
Abstract
1129 - Aspirin and Ticagrelor for the prevention of tumour cell induced platelet aggregation
Presenter: Meera Chauhan
Session: Poster Display session 3
Resources:
Abstract
4514 - Pharmacokinetic/ pharmacodynamic (PK/PD) exposure-response characterization of GSK3359609 (GSK609) from INDUCE-1, a phase I open-label study
Presenter: Michele Maio
Session: Poster Display session 3
Resources:
Abstract
5169 - In vitro functional interrogation of viable Circulating Tumor Associated Cells (C-TACs) for evaluating Platin resistance.
Presenter: Stefan Schuster
Session: Poster Display session 3
Resources:
Abstract
5827 - Targeting ARG2 as a novel therapeutic approach for cancer
Presenter: Marcin Grzybowski
Session: Poster Display session 3
Resources:
Abstract
3129 - MPS1 and PLK1 as new therapy targets in TP53 mutated solid tumors
Presenter: Balazs Gyorffy
Session: Poster Display session 3
Resources:
Abstract
2129 - The Tumor Static Exposure (TSE) concept & utility: application to combination treatment of radiation and radiosensitizing agent in tumor xenograft experiments
Presenter: Samer El Bawab
Session: Poster Display session 3
Resources:
Abstract
1814 - General Methodology to Optimize Tumor Treating Fields Delivery Utilizing Numerical Simulations
Presenter: Noa Urman
Session: Poster Display session 3
Resources:
Abstract
3010 - The Australian Exceptional Responders Program: a National collaboration
Presenter: Megan Barnet
Session: Poster Display session 3
Resources:
Abstract