Immunotherapy for NSCLC
Abstract
It is estimated that 158,000 Americans will die of lung cancer in 2015. This amounts to 433 deaths per day, more than breast, prostate, colorectal, and pancreatic cancer combined. Despite advancement of non-small cell lung cancer (NSCLC) treatments, little progress has been made on extending the 5-year survival rate of lung cancer patients over the past 30 years. There is significant room for improvement. Active duty military and Veterans are at a higher risk for lung cancer than the civilian population. This is due a number of factors including higher smoking rates (33% vs. 20%) and exposure to chemical carcinogens on the job. The Department of Veterans Affairs (VA) has initiated yearly CT scanning of patients at high risk for lung cancer, which has resulted in earlier detection. Yet, there remains a critical need for therapeutics that are successful, safe, and cost-effective. Most therapeutic regimens involve toxic compounds, which exert their effects on both the tumor and healthy tissue. As a result, chemotherapeutics are often given at the maximum tolerated dose, not the dose that is most effective at killing the tumor. Additionally, resistance to the drug often occurs, at which point patients and families are faced with the heartbreaking news that tumors that were previously shrinking or undetectable are now growing again. For these reasons, efforts have been placed on harnessing the power of the patient s immune system to recognize and destroy tumor cells, in the same fashion that the immune system neutralizes infectious disease. Now imagine we can take it one step further -- what if we can harness the immune response from childhood vaccines to eliminate NSCLC tumors? We propose a three-component system that can stimulate the immune system to attack lung tumor cells, which can be broken down as follows: (1) The first component is a small peptide (part of a larger protein) that comes from a virus such as measles or smallpox. It is this peptide that the immune system will recognize as "foreign." This peptide is chosen because it can be displayed on the surface of a cell and make the cell look like it is infected with virus. Scientists call this an immunogenic or antigenic peptide. (2) The immunogenic peptide will be encapsulated in a spherical microscopic 100-nanometer "fat spheres" called liposomes. This protects the antigenic peptide as it circulates in the body and hides it from the immune system while it is transported to the tumor. (3) The outside of the liposome will be decorated with a second peptide. This peptide has two special functions. It is a "targeting" peptide that can bind specifically to lung cancer cells but doesn t recognize normal cells. This is critical as the therapy should go only to the tumor but no other healthy tissues. Once the targeting peptide docks on the lung cancer cell, it serves its second function: it triggers uptake of the liposome and delivers it to the right location inside the cell. Once the liposome is inside the lung cancer cell, the cell will process the delivered immunogenic peptide and transport it to the surface of the cell in a specialized protein. This "marks" the cell and alarms the immune system. Basically, we are trying to trick the immune system into thinking that cancer cells are infected with measles without actually using measles virus. If the patient has been vaccinated against the virus, s/he has a specialized set of immune cells called memory T cells that rapidly expand and mount an immune response if it detects a cell that is infected with the virus. In this case, the cancer cell appears infected. The net result of this type of immune response is destruction of the cancer cell. This approach has two features that make it particularly well-suited for active Service members and Veterans diagnosed with lung cancer. (1) In order for therapy to be effective, the patient must have been previously vaccinated for measles and/or smallpo
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610262
Entities
People
- Kathlynn Brown
Organizations
- SRI International
- United States Army