Abstract

Cancer vaccines have always been a subject of gene therapy research. One of the most successful approaches has been working with genetically modified tumor cells. In this study, we describe our approach to achieving an immune response against a murine melanoma model, employing B16 tumor cells expressing GM-CSF and B7.2. Wild B16 cells were injected in C57BL6 mice to cause the tumor. Irradiated B16 cells transfected with GM-CSF, B7.2, or both, were processed as a preventive and therapeutic vaccination. Tumor volumes were measured and survival curves were obtained. Blood samples were taken from mice, and IgGs of each treatment group were also measured. The regulatory T cells (Treg) of selected groups were quantified using counts of images taken by confocal microscopy. Results: one hundred percent survival was achieved by preventive vaccination with the group of cells transfected with p2F_GM-CSF. Therapeutic vaccination achieved initial inhibition of tumor growth but did not secure overall survival of the animals. Classical Treg cells did not vary among the different groups in this therapeutic vaccination model.

Highlights

  • There is increasing evidence of the importance of immunotherapy in the fight against cancer.Currently, certain cytokines are being used as adjuvants in the treatment of some types of cancer.Melanoma is possibly the best candidate for immunotherapy as an alternative to current treatments because it is a very immunogenic type of malignancy.In the field of immunotherapy, antitumor vaccines are one of the most promising therapeutic strategies

  • The present study describes the efficacy of the GM-CSF transfected cells vaccine, and the effect of this cytokine in combination with the costimulator molecule B7.2, with a view to determining whether there is some kind of synergy between them

  • The best results were obtained with groups B16-GM-CSF, B16-pMok_GM-CSF, and B16-GM-CSF + B7.2/200, where there was no visible development of the tumor implanted during the measurement period—a time in which mice from other groups had already begun to die as a result of tumor development

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Summary

Introduction

There is increasing evidence of the importance of immunotherapy in the fight against cancer.Currently, certain cytokines are being used as adjuvants in the treatment of some types of cancer.Melanoma is possibly the best candidate for immunotherapy as an alternative to current treatments because it is a very immunogenic type of malignancy.In the field of immunotherapy, antitumor vaccines are one of the most promising therapeutic strategies. There is increasing evidence of the importance of immunotherapy in the fight against cancer. Certain cytokines are being used as adjuvants in the treatment of some types of cancer. Melanoma is possibly the best candidate for immunotherapy as an alternative to current treatments because it is a very immunogenic type of malignancy. The cytokine GM-CSF (granulocyte and macrophage colony stimulating factor) has demonstrated a very important antitumor effect [14,15,16,17,18,19,20,21,22,23,24,25,26,27,28]. GM-CSF is produced by a wide range of cell types, and its main functions are to stimulate the proliferation, maturation, and function of APCs (Antigen Presenting Cells) [29], facilitating their presentation of antigen to T cells, and contributing in this way to the immune cellular response against tumors

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