Combined p14ARF and Interferon-β Gene Transfer to the Human Melanoma Cell Line SK-MEL-147 Promotes Oncolysis and Immune Activation

Current Status of Canine Melanoma Diagnosis and Therapy: Report From a Colloquium on Canine Melanoma Organized by ABROVET (Brazilian Association of Veterinary Oncology)

“…However, IFNβ is known to function in a species-specific manner (47,48); therefore, it is imperative to test our approach in relevant models. Recent work using human cDNAs and established human melanoma cell lines produced a similar result, where cell killing was even more efficient and continued to be associated with the expression of ICD markers (49,50). Strikingly, an ex vivo model using human SK-MEL-147 cells was used to show that cell death induced by our treatment activated human dendritic cells that caused priming of T cells to induce a cytolytic response on encountering naïve tumor cells (50).…”

“…Recent work using human cDNAs and established human melanoma cell lines produced a similar result, where cell killing was even more efficient and continued to be associated with the expression of ICD markers (49,50). Strikingly, an ex vivo model using human SK-MEL-147 cells was used to show that cell death induced by our treatment activated human dendritic cells that caused priming of T cells to induce a cytolytic response on encountering naïve tumor cells (50). Thus, we have shown that our gene transfer approach promotes oncolysis and immune activation and can be considered as an immunotherapy.…”

It’s Getting Complicated—A Fresh Look at p53-MDM2-ARF Triangle in Tumorigenesis and Cancer Therapy

“…The reduced benefit of cancer immunotherapy can be attributed to altered tumorimmune microenvironment and compromised immune cell functions. With previous studies demonstrating ARF's ability to activate innate and adaptive immune responses within cancer cells to suppress tumorigenesis in vivo, ARF-targeting strategies present opportunities to augment existing cancer immunotherapies (Yetil et al, 2015;Cerqueira et al, 2020).…”

“…Strategies to develop ARF-based therapies have so far been limited to gene therapy and therapeutic peptides. Adenovirusmediated delivery of ARF had mostly been used experimentally in vitro, until recent studies showing its potential application using in vivo mouse cancer models (Saadatmandi et al, 2002;Tango et al, 2002;Cerqueira et al, 2020). This approach is expected to encounter similar obstacles faced by other gene therapies, including safety concerns and regulatory challenges, before reaching clinics (AuthorAnonymous, 2021).…”

Nonreplicating Adenoviral Vectors: Improving Tropism and Delivery of Cancer Gene Therapy

“…We have taken great care to use different models to demonstrate the functionality of our approach since it involves IFN-β, which is known to have species-specific activities [ 62 ]. To examine our approach in human melanoma cell lines, we used the AdRGD-PG backbone to construct vectors encoding the human cDNAs p14ARF and hIFN-β and showed immunogenic cell death characterized by the emission of critical markers in vitro as well as successful ex vivo priming of human T-cells [ 63 ].…”