Abstract 4170
Background
Among the most interesting targets for immunotherapeutic approaches, the Chondroitin Sulfate Proteoglycan (CSPG)4 stands out, with low expression in healthy tissues, high expression in several solid tumors and a key role in cancer progression. Because of the translational power of dogs as pre-clinical models for human malignancies and the CSPG4 over-expression by both human and canine malignant melanoma (MM), we demonstrated the safety and the clinical effectiveness of a xenogeneic human (Hu)-CSPG4 DNA vaccine in client-owned canine patients with stage II-III surgically resected CSPG4+ MM. However, Hu-CSPG4 vaccine was barely effective in activating human T cells from healthy donors in vitro. Based on these results, we aimed to increase the translational power of our approach and to extend it for the treatment of CSPG4+ tumors other than MM.
Methods
We generated a hybrid plasmid, derived in part from the Hu- and in part from the dog (Do)-CSPG4 sequences (HuDo-CSPG4). We tested the safety, immunogenicity and anti-tumor potential of HuDo-CSPG4 DNA vaccine in mice, in dogs with stage II-IV surgically resected CSPG4+ MM and in a human setting in vitro. We evaluated the potential of CSPG4-immune-targeting also for osteosarcoma (OSA).
Results
Chimeric HuDo-CSPG4 vaccination is strongly immunogenic in mice. In canine patients, the procedure is safe and induces antibodies (Ab) against both Hu- and Do-CSPG4, with a higher affinity and anti-tumor potential as compared to Hu-CSPG4. Clinically, HuDo-CSPG4 is effective in increasing the overall survival of vaccinated canine MM patients as compared to controls. Data obtained in vitro with T cells from human healthy donors suggest HuDo-CSPG4 is more immunogenic than Hu-CSPG4. Moreover, CSPG4 over-expression was demonstrated in human and canine OSA. Interestingly, anti-CSPG4 specific monoclonal Ab and sera derived from CSPG4 vaccinated canine MM patients showed to significantly inhibit human and canine CSPG4+ OSA cell proliferation, migration and osteospheres generation.
Conclusions
These results provide the rationale to propose HuDo-CSPG4 vaccination for the treatment of canine CSPG4+ tumors, to be successfully translated in a human setting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Federica Cavallo.
Funding
Associazione Italiana per la Ricerca sul Cancro (AIRC), Italian Ministry of Health.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2171 - CCND1 Amplification Contributes to Immunosuppression in Head and Neck Squamous Cell Carcinoma and the Association with a Poor Response to Immune Checkpoint Inhibitors
Presenter: Chloe Huang
Session: Poster Display session 3
Resources:
Abstract
2624 - Efficacy of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer patients with sensitive genes mutation
Presenter: Hui-Juan Cui
Session: Poster Display session 3
Resources:
Abstract
3494 - Neutrophil to Lymphocyte Ratio (NLR) kinetics as predictors of outcomes in metastatic renal cell carcinoma (mRCC) and non-small cell lung cancer (NSCLC) patients treated with nivolumab (N).
Presenter: Audrey Simonaggio
Session: Poster Display session 3
Resources:
Abstract
3964 - Predictive markers of checkpoint inhibitor activity in adult metastatic solid tumours
Presenter: Alexandra Pender
Session: Poster Display session 3
Resources:
Abstract
3041 - Blood-based TMB (bTMB) correlates with tissue-based TMB (tTMB) in a multi-cancer Phase I IO Cohort
Presenter: Daniel Araujo
Session: Poster Display session 3
Resources:
Abstract
3910 - Analysis of Molecular Profile Complexities for Immunotherapy Decision Support
Presenter: Robert Dóczi
Session: Poster Display session 3
Resources:
Abstract
4836 - The Role of Tumor Neoantigens in the Differential Response to Immunotherapy (IO) in EGFR and BRAF Mutated Lung Cancers - Quantity or Quality?
Presenter: Katrina Case
Session: Poster Display session 3
Resources:
Abstract
1929 - Impact of previous corticosteroid (CS) exposure on efficacy of Programmed Cell Death-(Ligand) 1 blockade in patients with advanced Non-Small-Cell Lung Cancer (NSCLC): a single Center retrospective analysis
Presenter: Fabrizio Nelli
Session: Poster Display session 3
Resources:
Abstract
2601 - Comparison 18F-FDG-PET/CT criteria for prediction of therapy response and clinical outcome in patients with metastatic melanoma treated with Ipilimumab and PD-1 inhibitors
Presenter: Sabrina Vari
Session: Poster Display session 3
Resources:
Abstract
3628 - Predictive model for survival in advanced non-small-cell lung cancer (NSCLC) treated with frontline pembrolizumab
Presenter: Xabier Mielgo Rubio
Session: Poster Display session 3
Resources:
Abstract