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
4868 - Evaluation of markers associated with efficacy of abiraterone acetate plus prednisone (AAP) in patients (pts) with castration-sensitive prostate cancer (mCSPC) from the LATITUDE study
Presenter: Kim Chi
Session: Poster Display session 3
Resources:
Abstract
4837 - LRP2, a potential new biomarker for Chinese younger aged intrahepatic cholangiocarcinoma patients
Presenter: Xiaoliang Shi
Session: Poster Display session 3
Resources:
Abstract
1286 - Reanalysis of the efficacy of molecular targeted agents (MTAs) given in the randomized trial SHIVA01 according to the ESMO ESCAT scale of actionability
Presenter: Aurelie Moreira
Session: Poster Display session 3
Resources:
Abstract
2736 - Comparison of Platforms for Determining Tumor Mutational Burden (TMB) From Blood Samples in Patients With Non-Small Cell Lung Cancer (NSCLC)
Presenter: Jonathan Baden
Session: Poster Display session 3
Resources:
Abstract
5045 - Comprehensive Pan-Cancer analysis of somatic mutations in drug transporters to reveal acquired and intrinsic drug resistance in 3149 metastatic cancer patients
Presenter: Sander Bins
Session: Poster Display session 3
Resources:
Abstract
4577 - Pan-Cancer Genomic Landscape of the Cyclin D1/FGF3,4,19 (11q13) Amplicon Including Associations with HPV Status, and ESR1 and AR Alterations
Presenter: Jennifer Johnson
Session: Poster Display session 3
Resources:
Abstract
5366 - Co-occurrence of NTRK fusions with other genomic biomarkers in cancer patients
Presenter: Xiaolong Jiao
Session: Poster Display session 3
Resources:
Abstract
4084 - Prospective comparative study of next-generation sequencing on fine needle aspirations versus core needle biopsies in cancer patients included in SHIVA02 trial
Presenter: Julien Masliah-Planchon
Session: Poster Display session 3
Resources:
Abstract
6017 - First national External Quality Assessement for the interpretation of somatic variants: assessment of 25 variants in colorectal, lung, ovarian cancers and melanoma in France
Presenter: Etienne Rouleau
Session: Poster Display session 3
Resources:
Abstract
2283 - Prospective testing of circulating tumor DNA in metastatic breast cancer facilitates clinical trial enrollment and precision oncology
Presenter: Andjelija Bujak
Session: Poster Display session 3
Resources:
Abstract