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
4489 - A Window of Opportunity Trial of Atorvastatin Targeting p53 Mutant Malignancies
Presenter: Joaquina Baranda
Session: Poster Display session 3
Resources:
Abstract
1945 - Randomized Phase II Study of Trabectedin/Olaparib Compared to Physician’s Choice in Subjects with Previously Treated Advanced or Recurrent Solid Tumors Harboring DNA Repair Deficiencies.
Presenter: Christoph Heilig
Session: Poster Display session 3
Resources:
Abstract
3021 - Homogenisation of Leftover Surgical Tissue across multiple cancer types: a Feasibility Study (HoLST-F)
Presenter: Lavinia Spain
Session: Poster Display session 3
Resources:
Abstract
2882 - Safety, efficacy, and immune effects of intratumoral tilsotolimod in patients with refractory solid tumors: updated results from ILLUMINATE-101
Presenter: Hani Babiker
Session: Poster Display session 3
Resources:
Abstract
1950 - Phase 1 Dose Escalation of MSC-1, a humanized anti-LIF monoclonal antibody, in patients (pts) with advanced solid tumors: Updated results
Presenter: Erkut Borazanci
Session: Poster Display session 3
Resources:
Abstract
2391 - A phase 1 study of Sym021, an anti-PD-1 antibody (Ab), alone and in combination with Sym022 (anti-LAG-3) or Sym023 (anti-TIM-3)
Presenter: Anna Spreafico
Session: Poster Display session 3
Resources:
Abstract
5692 - FPA150 (B7-H4 antibody) Phase 1 Update in Advanced Solid Tumors: Monotherapy and in Combination with Pembrolizumab
Presenter: Zev Wainberg
Session: Poster Display session 3
Resources:
Abstract
2416 - MG1124, a novel CEACAM1-targeted monoclonal antibody, has therapeutic potential as a combination partner of PD-1 inhibitors in NSCLC patients
Presenter: Eun Hee Lee
Session: Poster Display session 3
Resources:
Abstract
2661 - Tumor stroma targeting and modulation by OMTX705 ADC, a novel and potent immunotherapeutic treatment of solid tumors.
Presenter: Myriam Fabre
Session: Poster Display session 3
Resources:
Abstract
3681 - Durvalumab + monalizumab, mFOLFOX6, and bevacizumab in patients (pts) with metastatic microsatellite-stable colorectal cancer (MSS-CRC)
Presenter: May Cho
Session: Poster Display session 3
Resources:
Abstract