A Novel Immune-Modulating Antibody for the Treatment of Lung Cancer
Abstract
Scientific Objective and Rationale: This project fits within the Lung Cancer Research Program Area of Emphasis: “Identify innovative strategies for prevention and treatment of early and/or localized lung cancer.” We are developing a new approach to treatment of lung cancer, based on observations of the body’s immunological response. We have discovered that many people with early-stage non-small-cell lung cancer (NSCLC) make antibodies to a protein called CFH that protects tumor cells from destruction from the complement system. The complement system is part of the immune system, consisting of proteins found in blood that poke holes in cells, causing them to die. We proposed that patients with CFH antibodies do not develop metastasis because these antibodies neutralize the CFH, allowing complement to destroy tumor cells before they can metastasize. We have now cloned and expressed a human CFH antibody with the aim of developing a new lung cancer therapy. This antibody kills lung cancer cells and inhibits the growth of a tumor growing in a mouse. We have also seen that tumors treated with the CFH antibody are infiltrated with immune cells. Our rationale for the current project is that a therapeutic antibody that not only kills tumor cells directly but also stimulates antitumor immunity can produce long-term patient survival. Our scientific objectives are to study the effect of the CFH antibody on both the short-term and long-term immune response to the tumor in mice and to conduct a study of factors in humans that may predict which subset of patients will respond best to CFH antibody treatment. Applicability: Types of patients the research will help: This research will help patients with lung cancer. Currently, patients with early-stage NSCLC receive surgery, but often no chemotherapy; however, about half of these patients will experience recurrence. One potential use of the CFH antibody is as a preventative drug against recurrence in all early-stage patients. Patients with more advanced-stage lung cancer usually receive chemotherapy since their cancer has already spread. These patients could also be helped by receiving the CFH antibody as a treatment. The antibody is expected to be much less toxic and more effective than current chemotherapy. Potential clinical applications, benefits, and risks: We expect the benefits of the CFH antibody to be prevention of metastasis and abolition of cancer with few side effects, as people who naturally produce similar antibodies have no negative reactions attributable to them. There is a need for a wider variety of cancer drugs, and the CFH antibody works by a mechanism unlike that of any other cancer drug currently in use and is expected to have no significant side effects. Projected time it may take to achieve a clinically relevant outcome: We intend to enter our antibody into a Phase I clinical trial in 2019. Likely contributions of this study to advancing the field of lung cancer research: In addition to developing a unique therapy, this work would shed light on the potential for exploitation of the complement system in attacking cancer and might be the springboard for additional immunotherapy studies. Relevance to military Service members, Veterans, and their families: The project is relevant to military Service members, Veterans, and their families who suffer from lung cancer because current treatments are inadequate and new treatments are urgently needed. This is especially the case because of the high rates of lung cancer in this population.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910341
Entities
People
- Edward Patz
Organizations
- Duke University
- United States Army