How to kick-start the immune response in anti-tumor therapy? a unique screening platform to identify ICD inducers.

Immunological cell death (ICD) is a form of cancer cell death induced by radiotherapy, photodynamic therapy and chemotherapeutic agents. Unlike apoptosis or necrosis, ICD can induce an effective immune response directed against the tumor whereby both dendritic cells and T lymphocytes are mediators of this response. Dying cancer cells recruit and activate immune cells by releasing damage-associated molecular patterns (DAMPs).

Using our in-house developed screening strategy facilitated by an in vitro platform with four assays, we have identified and characterized several ICD inducers and a Nanocyclix compound for the three key DAMPs and cell viability in several cell lines. Evaluation of phagocytosis and cytokine levels showed that ICD activates both innate and adaptive arms of the immune system. With respect to cancer immunotherapy, the ICD process elicits enhanced adjuvanticity and antigenicity from dying cancer cells and consequently, promotes the development of clinically desired antitumor immunity.

In essence, we describe a novel strategy for the identification of ICD inducers within large chemical libraries followed by ex-vivo co-culture assays to demonstrate enhanced DC and T cell function.

Key learning objectives:

•Introduction to ICD

•How Oncodesign can help you to identify / characterize ICD inducers

•Case study