Related Experiment Video
Updated: Feb 9, 2026
Evaluation of the In vivo Antitumor Activity of Polyanhydride IL-1α Nanoparticles
Published on: June 28, 2021
Melanoma protective antitumor immunity activated by catalytic DNA
Hong Cai1, Eun-Ae Cho2, Yue Li1
1Vascular Biology and Translational Research, School of Medical Sciences & UNSW Medicine, The University of New South Wales, Sydney, NSW, 2052, Australia.
Abstract:
Melanoma incidence is increasing worldwide, and although drugs such as BRAF/MEK small-molecule inhibitors and immune checkpoint antibodies improve patient outcomes, most patients ultimately fail these therapies and alternative treatment strategies are urgently needed. DNAzymes have recently undergone clinical trials with signs of efficacy and no serious adverse events attributable to the DNAzyme. Here we investigated c-Jun expression in human primary and metastatic melanoma. We also explored the role of T cell immunity in DNAzyme inhibition of primary melanoma growth and the prevention of growth in non-treated tumors after the cessation of treatment in a mouse model. c-Jun was expressed in 80% of melanoma cells in human primary melanomas (n = 17) and in 83% of metastatic melanoma cells (n = 38). In contrast, c-Jun was expressed in only 11% of melanocytes in benign nevi (n = 24). Dz13, a DNAzyme targeting c-Jun/AP-1, suppressed both Dz13-injected and untreated B16F10 melanoma growth in the same mice, an abscopal effect relieved in each case by administration of anti-CD4/anti-CD8 antibodies. Dz13 increased levels of cleaved caspase-3 within the tumors. New, untreated melanomas grew poorly in mice previously treated with Dz13. Administration of anti-CD4/anti-CD8 antibodies ablated this inhibitory effect and the tumors grew rapidly. Dz13 inhibited c-Jun expression, reduced intratumoral vascularity (vascular lumina area defined by CD31 staining), and increased CD4+ cells within the tumors. This study provides the first demonstration of an abscopal effect of a DNAzyme on tumor growth and shows that Dz13 treatment prevents growth of subsequent new tumors in the same animal. Dz13 may be useful clinically as a therapeutic antitumor agent by preventing tumor relapse through adaptive immunity.
Insights
A novel DNAzyme, Dz13, targets c-Jun in melanoma, showing therapeutic promise. This treatment demonstrated an abscopal effect and prevented new tumor growth, suggesting potential for preventing melanoma relapse via adaptive immunity.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Melanoma incidence is rising globally, with current therapies like BRAF/MEK inhibitors and immune checkpoint antibodies facing treatment resistance.
- Alternative therapeutic strategies are crucial for managing melanoma, especially given the limitations of existing treatments.
- DNAzymes represent a promising class of therapeutic agents, with early clinical trials indicating efficacy and a favorable safety profile.
Purpose of the Study:
- To investigate the expression of c-Jun in human primary and metastatic melanoma.
- To explore the role of T cell immunity in DNAzyme-mediated inhibition of melanoma growth.
- To assess the potential of DNAzymes to prevent tumor growth in non-treated sites and subsequent new tumors.
Main Methods:
- Analysis of c-Jun expression in human melanoma and benign nevi samples.
- Treatment of B16F10 melanoma-bearing mice with Dz13, a DNAzyme targeting c-Jun/AP-1.
- Evaluation of tumor growth, abscopal effects, and adaptive immunity using anti-CD4/anti-CD8 antibodies.
- Assessment of cleaved caspase-3 levels, intratumoral vascularity, and immune cell infiltration.
Main Results:
- c-Jun was highly expressed in melanoma cells (80% primary, 83% metastatic) but minimally in benign melanocytes (11%).
- Dz13 suppressed growth of both treated and untreated melanomas, demonstrating an abscopal effect dependent on CD4+/CD8+ T cells.
- Dz13 treatment led to increased cleaved caspase-3, reduced tumor vascularity, and enhanced CD4+ T cell infiltration, with established protective immunity against new tumor formation.
Conclusions:
- This study demonstrates the first abscopal effect of a DNAzyme on tumor growth.
- Dz13 treatment establishes protective immunity, preventing the growth of subsequent tumors in the same animal.
- Dz13 holds potential as a therapeutic agent for melanoma, possibly preventing relapse through adaptive immunity.
More Related Videos
Related Concept Videos
01:31Active versus Passive Immunity
Active Immunity
Active immunity refers to the resistance one develops...
01:38What is the Immune System?
01:19Turnover Number and Catalytic Efficiency
Chymotrypsin is a pancreatic enzyme that breaks down proteins during digestion....
01:07Catalytically Perfect Enzymes
Most enzymes...
01:36Humoral Immune Responses
00:55DNA Helicases