Lung cancer is the most prevalent cancer worldwide and responsible for the most cancer deaths in the United States. Existing therapies include surgery, radiation, or chemotherapy to kill the tumor cells, but these options are not adequate for the vast majority of patients. Thus, there is a significant need to develop new therapeutic approaches. One of the most promising areas of development is immunotherapy, which reprograms the immune system to recognize and eliminate the tumor. We identified a protein that is expressed on lung cancer cells that may allow a tumor to evade the immune system by regulating the recruitment of host immune cells. Our goal is to develop a neutralizing antibody that will inhibit the activity of this protein and reactivate the anti- tumor immune response, resulting in tumor regression. We have produced monoclonal antibodies against this target. This first aim of this proposal is to characterize the antibodies in molecular and cellular assays to select the optimal antibody based upon binding the target and inhibiting its signaling activity. The second aim of the proposal will test the antibody in mouse tumor models and determine if the antibody inhibits tumor growth. This proposal is the foundation for development of an antibody for use as human therapeutics. If successful, it will result in a new treatment option tha will improve survival for patients with lung cancer.
Public Health Relevance Statement: Public Health Relevance: Lung cancer patients do not have adequate treatment options and most die within five years of diagnosis. We have identified a protein expressed on lung cancers which may recruit inhibitory immune cells, thus permitting unrestricted tumor growth. We are testing antibodies that block the activity of this protein to determine if they prevent tumor growth in animal models; if so, these antibodies have the potential to be developed into therapeutics for humans.
Project Terms: Affinity; Animal Model; Antibodies; Area; base; Binding (Molecular Function); Blocking Antibodies; cancer cell; Cancer Patient; CC chemokine receptor 1; CCL14 gene; CCR1 gene; CCR5 gene; Cells; Cellular Assay; Cessation of life; chemokine; Chemokine (C-C Motif) Receptor 5; chemokine receptor; chemotherapy; Clinical; Clinical Trials; cytokine; Data; Development; Diagnosis; Disease Outcome; drug development; Evaluation; Foundations; Goals; Government; Growth; Human; Immune; Immune response; Immune system; Immunologic Surveillance; Immunosuppressive Agents; Immunotherapy; improved; In Vitro; in vivo; inhibiting antibody; Killings; Location; Malignant neoplasm of lung; Malignant Neoplasms; Mediating; migration; Minority; Modeling; Molecular; Monoclonal Antibodies; monocyte; Mortality Vital Statistics; Mus; neoplastic cell; neutralizing antibody; Non-Small-Cell Lung Carcinoma; novel therapeutic intervention; Orthologous Gene; Patients; Peptide Hydrolases; Persons; Play; Population; pressure; prevent; Primary Neoplasm; Process; Proteins; public health relevance; Radiosurgery; Recruitment Activity; research study; Role; Signal Transduction; standard of care; Survival Rate; System; T-Cell Activation; T-Lymphocyte; Testing; Therapeutic; Therapeutic Agents; Tissues; tumor; Tumor Burden; tumor growth; tumor progression; United States; Validation; Work
