Biohybrid Vaccines for Improved Treatment of Aggressive Melanoma with Checkpoint Inhibitor

Abstract

Recent approaches in the treatment of cancer focus on involving the immune system to control the tumor growth. The administration of immunotherapies, like checkpoint inhibitors, has shown impressive results in the long term survival of patients. Cancer vaccines are being investigated as further tools to prime tumor-specific immunity. Biomaterials show potential as adjuvants in the formulation of vaccines, and biomimetic elements derived from the membrane of tumor cells may widen the range of antigens contained in the vaccine. Here, we show how mice presenting an aggressive melanoma tumor model treated twice with the complete nanovaccine formulation showed control on the tumor progression, while in a less aggressive model, the animals showed remission and control on the tumor progression, with a modification in the immunological profile of the tumor microenvironment. We also prove that co-administration of the nanovaccine together with a checkpoint inhibitor increases the efficacy of the treatment (87.5% of the animals responding, with 2 remissions) compared to the checkpoint inhibitor alone in the B16.OVA model. Our platform thereby shows potential applications as a cancer nanovaccine in combination with the standard clinical care treatment for melanoma cancers.

A Hybrid Eukaryotic–Prokaryotic Nanoplatform with Photothermal Modality for Enhanced Antitumor Vaccination

“…The design of hybrid biomimetic nanoplatforms has currently been explored by engineering fusion of eukaryotic cells or cytomembrane components, which accomplishes the development of biomimetic nanocarrier with integrated functions and allows the implantation of other therapeutic modalities. [ 9 ] Currently, immune cell (i.e., DCs, leukocytes) components are mainly employed as ingredients for fusion with CMVs to endow the binary nanoplatforms with the desired immune properties. [ 10 ] For example, a hybrid cytomembrane formulated with fusion of cancer cells and DCs has been reported to not only express tumor antigens, but also potentiate immune stimulation for antitumor vaccination.…”

Nanosystems for Improved Targeted Therapies in Melanoma

“…Cancer immunotherapy (passive or active) can specifically and persistently enhance the immune response to fight tumor cells. Over the years, promising results have been achieved in preclinical and clinical studies with several types of immunotherapeutic agents: monoclonal antibodies, immune checkpoint inhibitors, non-specific immunomodulatory agents, whole tumor cancer vaccines, and others [20,21].…”

“…Cancer immunotherapy can specifically and persistently enhance the immune response. A series of preclinical and clinical studies have explored the benefits of whole tumor cancer vaccines [20,21].…”

“…They can induce immunity against a wide variety of antigens [21] and can be obtained more easily compared to the selection of specific peptides [21]. The use of neoantigen vaccines for melanoma will probably be expanded in the future [35].…”

“…Tumor membrane-coated nanoparticles share some similarities with whole tumor vaccines, since they induce immune responses against multiple tumor antigens, without the need to select specific peptides [21].…”