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Regression of established B16F10 melanoma with a recombinant Listeria monocytogenes vaccine
Z K Pan1, L M Weiskirch, Y Paterson
1Department of Microbiology and the University of Pennsylvania Cancer Center, University of Pennsylvania, Philadelphia 19104-6076, USA.
Abstract:
We have previously shown that Listeria monocytogenes, a gram-positive, facultative intracellular bacterium, is a potent vector for targeting tumor-specific antigens to the immune system. In the present study, we extend these studies to the highly tumorigenic mouse melanoma B16F10, transduced with a model tumor antigen. We are able to induce the regression of primary tumors and established lung metastases by parenteral immunization with a L. monocytogenes recombinant that expresses the same antigen. Adjunctive therapy with granulocyte macrophage colony-stimulating factor or a vaccinia-based vaccine does not result in an improved cure rate over the L. monocytogenes vaccine alone. Tumor regression is accompanied by the expression of inflammatory cytokines in the tumor.
Insights
Listeria monocytogenes effectively targets tumor antigens for cancer immunotherapy. This bacterium can induce regression of melanoma tumors and lung metastases in mice, showing promise for cancer treatment.
Area of Science:
- Immunology
- Microbiology
- Oncology
Background:
- Listeria monocytogenes is a gram-positive bacterium with potential as a vaccine vector.
- Previous studies demonstrated its ability to target tumor antigens for immune system activation.
Purpose of the Study:
- To evaluate the efficacy of L. monocytogenes as a vector for targeting tumor antigens in a highly tumorigenic mouse melanoma model (B16F10).
- To assess the impact of L. monocytogenes-based immunotherapy on primary tumors and lung metastases.
Main Methods:
- Transduction of B16F10 melanoma cells with a model tumor antigen.
- Parenteral immunization of mice with a recombinant L. monocytogenes expressing the tumor antigen.
- Evaluation of adjunctive therapies including granulocyte macrophage colony-stimulating factor and a vaccinia-based vaccine.
Main Results:
- Parenteral immunization with recombinant L. monocytogenes induced regression of primary tumors and established lung metastases.
- Adjunctive therapies did not improve cure rates compared to L. monocytogenes vaccine alone.
- Tumor regression correlated with the expression of inflammatory cytokines within the tumor microenvironment.
Conclusions:
- Recombinant L. monocytogenes is a potent immunotherapy agent for mouse melanoma, capable of eradicating primary tumors and metastases.
- The efficacy of L. monocytogenes immunotherapy is not enhanced by adjunctive treatments with GM-CSF or a vaccinia-based vaccine.
- Tumor regression induced by L. monocytogenes is associated with an inflammatory cytokine response.