Cancer is a complex disease that evades the immune system through various mechanisms. The rapid proliferation of cells and their ability to resist therapy make cancer extremely aggressive. Solid tumors are particularly difficult to target because of their heterogeneity or complex assortment of characteristics. Specifically, the tumor encompasses a variety of different cancer cell types with different traits. Cancer cells also secrete pro-tumor proteins, which polarize and alter functions of healthy immune cells that would normally target the tumor. In this case, these altered immune cells promote tumor growth by supplying the cancer with nutrients and helping cancer cells travel to other sites of the body, known as metastasis. However, a major barrier to immunotherapy includes the lack of specific identifiable markers that differentiate the cancer from healthy cells and tissues.
Cancer surface markers help immune cells, known as T cells, identify and target the malignancy. The lack of identifiable markers limits therapeutic efficacy and the ability for the immune system to act on the tumor. The inability to accurately target cancer cells also leads to poor treatment specificity and off-target toxicity. As a result, scientists and researchers are looking into ways to boost tumor proteins or antigens, which identify them as foreign and elicit robust immunity.
A recent article in Nature, by Dr. Shuo Han and others, have identified a process that will amplify tumor markers and improve cancer therapeutic efficacy. Han is a principal investigator at the Shanghai Institute of Biochemistry and Cell Biology (SIBCB) in Shanghai, China. Han’s work focuses on various aspects of research using MultOmic and functional molecular labeling tools to conduct research and develop therapies. Specifically, he leverages the labeling of different substrates in cells to develop novel therapeutic approaches.
Han and his team have developed a strategy to engineer novel cell-surface proteins to be recognized by the immune system. This process is known as Proximity Amplification and Tagging of Cytotoxic Haptens or ‘PATCH’. The PATCH technique applies the process of proximity labeling, which is used to detect spatial relationships among proteins. In this study, researchers used PATCH to boost the number of cancer cell surface markers. Specifically, a specialized protein was delivered to the surface of the tumor and activated by red light. Consequently, a high-density of surface markers or antigens were generated on the tumor.
The PATCH-strategy led to a robust anti-tumor immune response. Additionally, the combination of PATCH with an immunotherapy enhanced therapeutic efficacy. Researchers tested this combination regimen in multiple cancer models and found significant anti-tumor effects. The treatment triggered a systemic immune response and eliminated tumors. Systemic immunity helped to target tumors in distal locations of the body and established immunological memory, which protects the body from further tumor recurrence.
Han and his team are the first to expand PATCH from a detection tool to a therapeutic treatment. Moreover, their successful amplification of tumor antigens is groundbreaking. It overcovers a crucial barrier to cancer therapy and will provide an alternative treatment for patients with cancer. Overall, this work enhances immunotherapy treatment and has the potential to significantly improve patient prognosis.