In situ administration of cytokine combinations induces tumor regression in mice
Jinyu Zhang1, Haochen Jiang2, Haiyun Zhang3
1Mianyi Biotech Corporation, Chongqing 401332, China.
Background:
Recent advances in cancer immunotherapy suggest a possibility of harnessing the immune system to defeat malignant tumors, but the complex immunosuppressive microenvironment confines the therapeutic benefits to a minority of patients with solid tumors.
Methods:
A lentivector-based inducible system was established to evaluate the therapeutic effect of cytokines in established tumors. Intratumoral injection of certain cytokine combination in syngeneic tumor models was conducted to assess the therapeutic potentials.
Findings:
Doxycycline (Dox)-induced local expression of cytokine combinations exhibites a strong synergistic effect, leading to complete regression of tumors. Notably, IL12 + GMCSF+IL2 expression induces eradication of tumors in all mice tolerated with this treatment, including those bearing large tumors of ~15 mm in diameter, and generates intensive systemic antitumor immunity. Other combinations with similar immune regulatory roles also induce tumor elimination in most of mice. Moreover, intratumoral injection of chitosan/IL12 + GMCSF+IL2 solution induces a complete response in all the tested syngeneic tumor models, regardless of various tumor immunograms.
Interpretation:
Administration of certain cytokine combinations in tumor microenvironment induces a strong synergistic antitumor response, including the recruitment of large amount of immune cells and the generation of systemic antitumor immunity. It provides a versatile method for the immunotherapy of intractable malignant neoplasms. FUND: There is no external funding supporting this study.
Insights
Certain cytokine combinations, including IL-12, GM-CSF, and IL-2, effectively eradicate tumors and generate systemic immunity. This immunotherapy approach offers a versatile strategy for treating intractable solid tumors.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Cancer immunotherapy shows promise but is limited by immunosuppressive tumor microenvironments.
- Solid tumors often resist current immunotherapeutic strategies.
Purpose of the Study:
- To evaluate the therapeutic potential of cytokine combinations delivered via a lentivector-based inducible system in established tumors.
- To assess the efficacy of intratumoral cytokine therapy in syngeneic tumor models.
Main Methods:
- Established a lentivector-based inducible system for local cytokine expression in tumors.
- Administered specific cytokine combinations intratumorally in syngeneic mouse tumor models.
- Utilized chitosan-based solutions for intratumoral delivery of cytokine combinations.
Main Results:
- Doxycycline-induced local expression of cytokine combinations demonstrated strong synergistic antitumor effects, leading to complete tumor regression.
- Interleukin-12 (IL-12) plus Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) plus Interleukin-2 (IL-2) eradicated tumors in all treated mice, including those with large tumors (~15 mm).
- This combination also generated robust systemic antitumor immunity, and chitosan/IL-12 + GM-CSF + IL-2 solutions achieved complete responses in all tested models, irrespective of tumor immunophenotype.
Conclusions:
- Specific cytokine combinations induce potent synergistic antitumor responses by recruiting immune cells and generating systemic immunity.
- This approach provides a versatile and effective method for the immunotherapy of difficult-to-treat malignant neoplasms.
- Intratumoral delivery of cytokine combinations shows broad applicability across diverse tumor types.
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