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Xenogeneic DNA immunization in melanoma models for minimal residual disease
William G Hawkins1, Jason S Gold, Nathalie E Blachere
1Swim Across America Laboratory, Departments of Surgery & Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.
Introduction:
DNA immunization with xenogeneic genes encoding homologous antigens protects mice against tumor challenge with syngeneic melanoma in a lung metastasis model. The effect of xenogeneic human TRP-2 (hTRP2) DNA immunization on disease confined to an orthotopic site, the skin, and in a model of minimal residual disease that is relevant to a setting of adjuvant therapy for micrometastatic cancer is reported.
Methods:
Immunization and tumor challenge with B16F10LM3 melanoma were performed in C57BL/6 mice and in mice genetically deficient in MHC class I or II molecules. A melanoma variant of B16 with a predilection for lung metastasis was selected and used to challenge C57BL/6 mice. Tumor challenge in the footpad with the B16 variant was followed by local tumor growth and lung metastasis. The tumor-bearing distal extremities were surgically resected and mice were randomized to receive hTRP2 DNA immunization or no treatment. Approximately 3-5 weeks after surgical resection, lungs were harvested and metastases counted.
Results:
Xenogeneic DNA immunization with hTRP2 prevented tumor growth in the skin by a mechanism requiring CD4(+) and CD8(+) T cells but did not inhibit the growth of established tumors. Adjuvant immunization with hTRP2 DNA after resection significantly reduced lung metastases and decreased local recurrence rates after surgical resection.
Conclusions:
Xenogeneic DNA immunization with hTRP2 was effective in protecting mice from intradermal tumor challenge. Immunization prevented local recurrence and the development of metastases in a mouse model of minimal residual disease, supporting a role for DNA immunization against melanosomal antigens as an adjuvant to surgery in high-risk primary melanomas.
Insights
Xenogeneic DNA immunization using human TRP-2 (hTRP2) DNA prevented melanoma in mice and reduced lung metastases after surgery. This approach shows promise as an adjuvant therapy for high-risk melanomas.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- DNA immunization with xenogeneic genes offers protection against melanoma.
- Human TRP-2 (hTRP2) DNA immunization was investigated for its effects on localized and micrometastatic melanoma.
Purpose of the Study:
- To evaluate the efficacy of hTRP2 DNA immunization in preventing skin melanoma and reducing metastasis.
- To assess the role of hTRP2 DNA immunization as an adjuvant therapy after surgical resection in a minimal residual disease model.
Main Methods:
- C57BL/6 mice and MHC-deficient mice were immunized with hTRP2 DNA and challenged with B16F10LM3 melanoma.
- Tumor-bearing extremities were resected, followed by adjuvant hTRP2 DNA immunization or no treatment.
- Lung metastases were quantified to assess treatment efficacy.
Main Results:
- hTRP2 DNA immunization prevented tumor growth in the skin, dependent on CD4(+) and CD8(+) T cells.
- Adjuvant immunization significantly reduced lung metastases and local recurrence rates post-surgery.
- Established tumors were not inhibited by the immunization.
Conclusions:
- Xenogeneic hTRP2 DNA immunization effectively protected against intradermal melanoma challenge.
- Adjuvant immunization prevented recurrence and metastasis in a minimal residual disease model.
- DNA immunization against melanosomal antigens may serve as an adjuvant to surgery for high-risk melanomas.