Oncolytic Viruses, Bi-specific T Cell Engagers and CAR-T Cells: A Promising Triple Combination Therapy for Pancreatic Ductal Adenocarcinomas

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignant cancer of the pancreas, with less than 5 percent of patients surviving five years after diagnosis. Due to the lack of early symptoms, initial diagnosis is often difficult, leading to a metastatic disease that can no longer be cured by surgical removal. Alongside this, the conventional methods of cancer therapies, such as chemotherapy and radiotherapy, are not effective for PDACs. However, in recent years, three novel therapeutic agents for treatment of cancer have emerged: oncolytic viruses (OVs), bi-specific T-cell engagers (BiTEs), and chimeric antigen receptor (CAR) T cells. Oncolytic virus treatments involve the use of viral replication cycles and viral tropism to target cancerous cells, and selectively kill them through lysis. Meanwhile, BiTEs allow the cytotoxic killing of cancer cells, including those that lack MHC expression, by linking tumor cells and cytotoxic T cells through bi-specific monoclonal antibodies. CAR-T cell immunotherapy utilizes the immune system to kill cancer cells by genetically modifying T cells to produce receptors targeted at specific cancer antigens. While all these therapies have had successes individually, problems have been associated with all of them for pancreatic cancer treatment. Recently, research has shown that oncolytic viruses can be engineered to encode and express BiTEs, targeting their expression to the cancerous cells. Combining this with CAR-T therapy provides a robust treatment with great therapeutic potential. This article will explore the use of oncolytic viruses, BiTEs and CAR-T cells as a treatment for PDACs, including the strengths and limitations of these treatments separately and as a combination therapy. Understanding how to combine these three therapeutic agents and target them to pancreatic cancer cells could result in a novel cancer therapy for PDACs, a cancer that currently does not have many promising treatments.