Abstract
Pancreatic adenocarcinoma (PA) is considered one of the most deadly types of cancer an individual can be afflicted with. PA leaves those inflicted with a relatively low chance of survival due to symptoms not being detected until it has already metastasized. Sadly, 7 5% of people with PA will die within a year after the cancer has been detected. Therefore, much attention should be given towards finding an alternative treatment for PA. Cancer cells creating the tumor are removed by radiation and/o~ chemotherapy leaving a subpopulation of cancer cells called cancer stem cells (CSC) behind. CSCs are defined as cells that have the capacity to self-renew and have the potential to proliferate indefinitely like other stem cells. CSCs are believed to be the reason for cancer patients relapsing post treatment after chemotherapy and/or radiation has been administered. Therefore, CSCs should be targeted for an effective treatment to be actualized for pancreatic cancer. Our lab utilized an FDA approved antibody called cetuximab that has already been implemented in phase I and phase II clinical trials. cetuximab was used to directly target CSC populations by binding directly to the over expressed cell surface marker, EGFR, on CSC populations. The tail end of the cetuximab antibody contains a segment called the Fe region that binds to specific immune cells. One type of immune cell of particular importance that binds to this Fe region of Cetuximab is a Natural Killer (NK) cell. NK cells are able to monitor the cells of the body through various activating and inhibitory receptors found on their cell surfaces. NK cells actively check for the presence of the major histocompatibility complex I (MHCI), which is detected by the NK cell's inhibitory receptor called the killer cell immunoglobulin-like receptor (KIR). MHCI is a cell surface protein that enables immune cells such as NK cells to recognize "self'-cells and prevent immune cells from destroying them. However, cancer cells as well as CSCs lack adequate amounts of MHCI that enables immune cells to identify and subsequently kill these cells. NK cells also have activating receptors, CD16, that can recognize the Fe portion of the antibody that signals to the NK cells to kill the cell attached to the antibody. This process is known as antibody directed cell mediated cytotoxicity (ADCC) and provides a means for a pinpointed attack on CSCs within a heterogeneous population of cells. We utilized this recognition and cytolytic property of NK cells with the use of cetuximab. Our treatment plan included the use of radiation to eliminate the non-CSC populations among the tumor followed by the administration of NK cells to the tumor site. NK cells then released their cytotoxic factors upon binding to the antibody which enabled a directed approach towards killing CSC populations. In addition, this treatment has the ability to treat other forms of cancer with CSC populations, providing potential hope to others suffering from other types of cancers.