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Updated: May 22, 2026
Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors
Published on: December 16, 2022
IL15 combined with Caspy2 provides enhanced therapeutic efficiency against murine malignant neoplasm growth and
1State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, The People's Republic of China.
Abstract:
Interleukin-15 (IL15) is a potential immunotherapeutic treatment for cancer. Caspy2 is an active zebra caspase for inducing apoptosis and immune response in murine tumors. In this study, we aim to evaluate the potential of gene therapy using IL15 and Caspy2 against the murine tumors. Plasmid expressing both Caspy2 and IL15 genes was constructed, encapsulated in DOTAP/cholesterol cationic liposome and injected intratumorally into the mice bearing CT26, B16-F10 and 4T1 carcinoma. We found that coexpression of IL15 and Caspy2 could significant inhibit tumor growth and prolong survival of the mice bearing CT26 or B16F10 tumor. A significant reduction in spontaneous lung metastasis was observed in the 4T1 tumor model. In CT26 model, the mice treated with IL15 and Caspy2 acquired a long-time protective immunity against the parental tumor cell rechallenge. Cytotoxic T lymphocytes and terminal deoxynucleotidyltransferase-mediated nick end labelling assays showed that the combination of capsy2 and IL15 could enhance both the apoptosis and immune response induction, which may account for its extraordinary antitumor effect. Furthermore, we showed that the observed tumor suppression by IL15 and Caspy2 concurred with the Caspy2-mediated downregulation of IL10 and upregulation of interferon-γ and tumor necrosis factor-α. Our results therefore suggested that the combination regimen might be a novel and effective strategy for cancer treatment.
Insights
Gene therapy combining Interleukin-15 (IL15) and Caspase Z (Caspy2) effectively inhibits tumor growth and metastasis in mice. This novel approach enhances apoptosis and immune response, offering a promising cancer treatment strategy.
Area of Science:
- Oncology
- Immunotherapy
- Gene Therapy
Background:
- Interleukin-15 (IL15) shows potential as an anti-cancer immunotherapeutic.
- Caspase Z (Caspy2) induces apoptosis and immune responses in murine tumors.
Purpose of the Study:
- To evaluate the efficacy of gene therapy using IL15 and Caspy2 against murine tumors.
- To assess the combined effect of IL15 and Caspy2 on tumor growth, metastasis, and immune response.
Main Methods:
- Constructed a plasmid expressing both Caspy2 and IL15 genes.
- Encapsulated the plasmid in DOTAP/cholesterol cationic liposomes for intratumoral injection.
- Administered the gene therapy to mice bearing CT26, B16-F10, and 4T1 carcinoma models.
Main Results:
- Coexpression of IL15 and Caspy2 significantly inhibited tumor growth and prolonged survival in CT26 and B16F10 models.
- Observed a significant reduction in lung metastasis in the 4T1 model.
- Demonstrated enhanced apoptosis and immune response induction, with Caspy2-mediated modulation of IL10, interferon-γ, and tumor necrosis factor-α.
Conclusions:
- The combination of IL15 and Caspy2 gene therapy exhibits significant antitumor effects in murine models.
- This regimen induces protective immunity and modulates key cytokines, suggesting a novel and effective cancer treatment strategy.
