Electrochemotherapy with cisplatin increases survival and induces immunogenic responses in murine models of lung cancer and colorectal cancer.

Electrochemotherapy is an emerging treatment modality for cancer patients which can effectively reduce tumour burden and induce immunogenic cell death. Electrochemotherapy is most commonly used with bleomycin as the drug of choice, here we examine the efficacy of electrochemotherapy with cisplatin. Electrochemotherapy with cisplatin was found to effectively reduce tumour growth in a range of murine models and induce significant intratumoural recruitment of myeloid and humoral immune cells. Following the observations of immune system mobilisation, we have shown an ability of electrochemotherapy to reduce metastatic potential as determined by tumour burden in the lung, and to exert an abscopal effect by reducing growth at distal untreated secondary tumours.

ICOS activation in combination with electrochemotherapy generates effective anti-cancer immunological responses in murine models of primary, secondary and metastatic disease.

Electrochemotherapy is an evolving therapy which has recently been shown to induce an immunogenic form of cell death. It is hypothesized that the immunogenic cell death induced by electrochemotherapy may compliment the responses seen with anti-cancer immunotherapies. We therefore examined the effect of electrochemotherapy in combination with ICOS activation, which promotes the activity of previously activated T cells. In comparison to either monotherapy which resulted in no curative outcomes in any model, in a CT26 primary tumour 50% of mice were cured, with 100% of cured mice surviving tumour rechallenge. In a dual flank CT26 model mimicking secondary disease 20% of mice were cured, and 30% of mice were cured using an aggressively metastatic Lewis Lung Carcinoma model. We have shown the novel combination of electrochemotherapy with ICOS activation can inhibit local and distal tumour growth, including total tumour clearance with long lasting immunological memory.

Local tumour ablative therapies: opportunities for maximising immune engagement and activation.

The relationship between cancer and the immune system is a complex one. The immune system can prevent tumour growth by eliminating cancer cells but this editing process ultimately results in poorly immunogenic cells remaining allowing for unchallenged tumour growth. In light of this, the focus of cancer treatment should be to maximise cancer elimination and the prevention of escape mechanisms. In this review we will examine current and emerging ablative treatment modalities that induce Immunogenic Cell Death (ICD), a special type of cell death that allows for immune cell involvement and the generation of an anti-tumour specific immune response. When paired with immune modulating agents, capable of potentiating the immune response and reversing the immune-suppressive environment created by tumours, we may be looking at the future of anti-cancer therapy.