This week we have focused on immunotherapy for melanoma. We reported on the results of a clinical trial using pembrolizumab, in addition to the personal experience of a patient taking part in a clinical trial. This article summarizes some of the latest developments in the field of immunotherapy for melanoma.
What is Immunotherapy?
Immunotherapy is a type of biological therapy. Immunotherapy enhances the ability of the immune system to kill cancer cells. There are two main types of immunotherapy. Active immunotherapy activates the body’s own immune system so that it will kill cancer cells, for example, a cancer vaccine. On the other hand, passive immunotherapy uses biologicals that are a part of the immune system as a treatment for killing cancer cells. An example of passive immunotherapy would be treatment using monoclonal antibodies. There are several kinds of immunotherapy currently in clinical trials for the treatment of advanced melanoma.
Bevacizumab is a monoclonal antibody currently being tested in a clinical trial by the National Cancer Institute, recruiting participants from over 400 study locations across the United States. Bevacizumab acts by blocking the protein VEGF, which is increased in cancer cells, and is involved in the formation of new blood vessels. In this way, bevacizumab potentially blocks the formation of new blood vessels that can support continued tumor growth. Bevacizumab will be administered to patients in combination with another monoclonal antibody used to treat melanoma, ipilimumab. The study will assess the effectiveness of the combination on inducing an immune response. Patients will be eligible to participate in the study if they are at least 18 years old, with stage III or IV melanoma, and have completed any prior treatment at least 4 weeks earlier.
A study by Caladrius Biosciences, Inc. is underway to assess the safety and effectiveness of a new therapy that aims to utilize patient-derived cells. Both tumor cells and specific immune cells, called dendritic cells, will be isolated from the patient. Researchers will grow the patients’ dendritic cells in the laboratory, using a growth factor called granulocyte-macrophage colony stimulating factor (GM-CSF). The dendritic cells will be grown together with the patient tumor cells, in an effort to enhance the ability of the dendritic cells to fight the cancer cells. The resulting mixture will then be injected back into the patient. The researchers will then determine the safety and effectiveness of the treatment in increasing survival in patients with melanoma. Participants are currently being recruited across the United States to take part in this study.
Investigators in the United Kingdom, in collaboration with Scancell Ltd. are investigating a potential DNA immunotherapy. The treatment for this study will be SCIB1, a solution of plasmid DNA that encodes an antibody. This antibody has been designed to stimulate the T cells of the patient to have a stronger, more specific effect on killing melanoma cells. The trial is designed to test the safety and effectiveness of this form of therapy in patients with stage III or IV melanoma. Patients will be injected with the SCIB1 solution 5 times over a period of 5.5 months. The follow up period will be for an additional 5 years following treatment.
A cancer vaccine, GeniusVac-Mel4, is being studied by researchers in France. The researchers aim to assess the safety and effectiveness of this vaccine at eliciting an immune response in patients with melanoma. The vaccine was previously shown to induce an immune response in mice, and in human peripheral blood mononuclear cells. Participants will be included in the trial if they are 18 years or older, with metastatic melanoma (stage IIC or IV), who have not responded to previous therapy.
Canadian Cancer Society Biological Therapy Fact Sheet. Available from: http://www.cancer.ca/en/cancer-information/diagnosis-and-treatment/chemotherapy-and-other-drug-therapies/biological-therapy/?region=on Last Accessed: July 3, 2015.
Clinicaltrials.gov “Ipilimumab With or Without Bevacizumab in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery” Available from: https://www.clinicaltrials.gov/ct2/show/NCT01950390?term=mab+AND+melanoma&recr=Open&no_unk=Y&rank=4 Last Accessed: July 3, 2015.
Clinicaltrials.gov “Autologous Dendritic Cell-Tumor Cell Immunotherapy for Metastatic Melanoma” Available from: https://www.clinicaltrials.gov/ct2/show/NCT01875653?term=melanoma+AND+immunotherapy&recr=Open&no_unk=Y&rank=2 Last Accessed: July 3, 2015.
Clinicaltrials.gov “Study of a DNA Immunotherapy to Treat Melanoma” Available from: https://www.clinicaltrials.gov/ct2/show/NCT01138410?term=melanoma+AND+immunotherapy&recr=Open&no_unk=Y&rank=3 Last Accessed: July 3, 2015.
Clinicaltrials.gov “Safety Study of a Dendritic Cell-based Cancer Vaccine in Melanoma (GeniusVac-Mel4)” Available from: https://www.clinicaltrials.gov/ct2/show/NCT01863108?term=melanoma+AND+immunotherapy&recr=Open&no_unk=Y&rank=5 Last Accessed: July 3, 2015.
Image courtesy of KROMKRATHOG at FreeDigitalPhotos.net
Written by Deborah Tallarigo, PhD