Three antigen-loading methods in dendritic cell vaccines for metastatic melanoma

Abstract

In the current era of checkpoint inhibitors, some patients with metastatic melanoma have shown a significant improvement in survival. However, optimization of immunotherapy is an ongoing effort. Monocyte-derived dendritic cell (MODC) vaccines have been shown in clinical trials to be safe and capable of inducing tumor-specific immunity as well as occasional objective clinical responses. Here, we conducted a three-arm pilot clinical study in 15 patients with metastatic melanoma to evaluate three types of MODC vaccines, differing only by strategies of tumor antigen delivery. MODCs were isolated from each patient and loaded with patients' own melanoma cells as sources of antigens. Antigen loading was achieved ex vivo by fusing melanoma cells with MODCs, co-culturing melanoma cells with MODCs, or by pulsing MODCs with melanoma cell lysates. The vaccines were then injected into superficial lymph nodes using high-resolution ultrasound guidance. Primary end points included delayed-type hypersensitivity responses and positive ELISpot result, which measures interferon-γ production. Five of 15 patients achieved delayed-type hypersensitivity responses and six of 15 patients had positive ELISpot results. We demonstrated that the vaccines were safe and well-tolerated by all patients and produced immunological responses in all arms. Although MODC vaccine monotherapy has limited efficacy, combining this vaccine with other immunotherapies, such as checkpoint inhibitors, to engage multiple components of the immune system may be an effective and viable future approach.