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Updated: May 11, 2026
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Antitumor activity of tumor-targeted RNA replicase-based plasmid that expresses interleukin-2 in a murine melanoma
B Leticia Rodriguez1, Jorge M Blando, Dharmika S P Lansakara-P
1Pharmaceutics Division, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, USA.
Abstract:
Double-stranded RNA (dsRNA) has multiple antitumor mechanisms that may be used to control tumor growth. Previously we have shown that treatment of solid tumors with a plasmid that encodes Sindbis viral RNA replicase complex, pSIN-β, significantly inhibited the growth of tumors in mice. In the present study, we evaluated the feasibility of further improving the antitumor activity of the pSIN-β plasmid by incorporating interleukin-2 (IL2) gene into the plasmid. The resultant pSIN-IL2 plasmid was delivered to mouse melanoma cells that overexpress the sigma receptor. Here we report that the pSIN-IL2 plasmid was more effective at controlling the growth of B16 melanoma in mice when complexed with sigma receptor-targeted liposomes than with the untargeted liposomes. Importantly, the pSIN-IL2 plasmid was more effective than pSIN-β plasmid at controlling the growth of B16 melanoma in mice, and B16 tumor-bearing mice that were treated with pSIN-IL2 had an elevated number of activated CD4(+), CD8(+), and natural killer cells, as compared to those treated with pSIN-β. The RNA replicase-based, IL2-expressing plasmid may have applications in melanoma gene therapy.
Insights
This study enhanced a plasmid for melanoma gene therapy. The new plasmid, pSIN-IL2, showed improved control of melanoma tumor growth in mice and boosted immune cell activity.
Area of Science:
- Immunology
- Molecular Biology
- Gene Therapy
Background:
- Double-stranded RNA (dsRNA) exhibits antitumor properties.
- Previous research demonstrated pSIN-β plasmid's efficacy in inhibiting solid tumor growth.
- Interleukin-2 (IL2) is a cytokine with immunomodulatory functions.
Purpose of the Study:
- To enhance the antitumor activity of the pSIN-β plasmid by incorporating the interleukin-2 (IL2) gene.
- To evaluate the efficacy of the modified pSIN-IL2 plasmid in controlling melanoma growth.
- To assess the immune response elicited by the pSIN-IL2 plasmid delivery.
Main Methods:
- Construction of the pSIN-IL2 plasmid by incorporating the IL2 gene into the pSIN-β plasmid.
- Delivery of the pSIN-IL2 plasmid to mouse melanoma cells using sigma receptor-targeted liposomes.
- Comparison of the antitumor efficacy of pSIN-IL2 with pSIN-β in a B16 melanoma mouse model.
- Analysis of immune cell populations (CD4+, CD8+, NK cells) in tumor-bearing mice.
Main Results:
- The pSIN-IL2 plasmid, complexed with sigma receptor-targeted liposomes, demonstrated superior control of B16 melanoma growth compared to untargeted liposomes.
- pSIN-IL2 significantly outperformed the original pSIN-β plasmid in inhibiting melanoma tumor growth.
- Treatment with pSIN-IL2 led to an increased number of activated CD4+, CD8+, and natural killer cells.
Conclusions:
- The RNA replicase-based, IL2-expressing plasmid (pSIN-IL2) represents an advancement in melanoma gene therapy.
- Targeted delivery of pSIN-IL2 enhances its efficacy in controlling melanoma.
- pSIN-IL2 therapy stimulates a potent anti-tumor immune response.
