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Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Tumor specific phage particles promote tumor regression in a mouse melanoma model
Fredrik Eriksson1, W David Culp, Robert Massey
1Department of Oncology and Pathology, Immune and Gene Therapy Laboratory, Cancer Centre Karolinska, Karolinska Institute, Stockholm, Sweden. fredrik.eriksson@ki.se
Abstract:
Within cancer research, phage display libraries have been widely used for the identification of tumor targeting peptides and antibodies. Additionally, phages are known to be highly immunogenic; therefore we evaluated the immunotherapeutic potential of tumor specific phages to treat established solid tumors in a mouse model of melanoma. We developed two tumor specific phages, one derived from a peptide phage display library and one Fab expressing phage with known specificity, for the treatment of mice bearing palpable B16-F10 or B16/A2K(b) tumors. Therapy in B16-F10 tumor bearing mice with tumor specific phages was superior to treatment with non-tumor specific phages and lead to delayed tumor growth and increased survival. In B16/A2K(b )tumor bearing mice, therapy with tumor specific phages resulted in complete tumor regression and long-term survival in 50% of the mice. Histological analysis of tumors undergoing treatment with tumor specific phages revealed that phage administration induced a massive infiltration of polymorphonuclear neutrophils. Furthermore, phages induced secretion of IL-12 (p70) and IFN-gamma as measured in mouse splenocyte culture supernatants. These results demonstrate a novel, immunotherapeutic cancer treatment showing that tumor specific phages can promote regression of established tumors by recruitment of inflammatory cells and induction of Th1 cytokines.
Insights
Tumor-specific phages show immunotherapeutic potential against melanoma. Treatment with these engineered phages led to delayed tumor growth, increased survival, and complete tumor regression in a mouse model.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Phage display libraries are crucial for identifying tumor-targeting peptides and antibodies in cancer research.
- Phages possess inherent immunogenic properties, suggesting their potential utility in immunotherapy.
Purpose of the Study:
- To evaluate the immunotherapeutic potential of tumor-specific phages for treating established solid tumors.
- To assess the efficacy of engineered phages in a mouse model of melanoma.
Main Methods:
- Development of two tumor-specific phages: one from a peptide phage display library and one Fab-expressing phage.
- Treatment of mice bearing B16-F10 or B16/A2K(b) melanoma tumors with tumor-specific phages.
- Histological analysis and measurement of cytokine secretion (IL-12, IFN-gamma) in splenocyte cultures.
Main Results:
- Tumor-specific phages significantly outperformed non-specific phages in delaying tumor growth and increasing survival in B16-F10 melanoma models.
- Complete tumor regression and long-term survival were observed in 50% of mice with B16/A2K(b) tumors treated with tumor-specific phages.
- Phage administration induced significant infiltration of polymorphonuclear neutrophils and secretion of Th1 cytokines (IL-12, IFN-gamma).
Conclusions:
- Tumor-specific phages represent a novel immunotherapeutic strategy for cancer treatment.
- Phage-based therapy can promote established tumor regression by recruiting inflammatory cells and inducing Th1 immune responses.
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