Abstract
Unlike traditional cancer therapies, such as surgery, radiation and chemotherapy that are typically non-specific, cancer immunotherapy harnesses the high specificity of a patient’s own immune system to selectively kill cancer cells. The immune system is the body’s main cancer surveillance system, but cancers may evade destruction thanks to various immune-suppressing mechanisms. We therefore need to deploy various immunotherapy-based strategies to help bolster the anti-tumour immune responses. These include engineering T cells to express chimeric antigen receptors (CARs) to specifically recognise tumour neoantigens, inactivating immune checkpoints, oncolytic viruses and dendritic cell (DC) vaccines, which have all shown clinical benefit in certain cancers. However, treatment efficacy remains poor due to drug-induced adverse events and immunosuppressive tendencies of the tumour microenvironment. Recent preclinical studies have unveiled novel therapies such as anti-cathepsin antibodies, galectin-1 blockade and anti-OX40 agonistic antibodies, which may be utilised as adjuvant therapies to modulate the tumour microenvironment and permit more ferocious anti-tumour immune response.
Highlights
Cancer remains a main global challenge due to the lack of early diagnosis, the inherent biological complexity of the tumour microenvironment (TME) and the unavailability of highly efficacious treatment strategies
This study presented a new method of treating haematological cancers without leading to the toxicities associated with chimeric antigen receptors (CARs) T-cell therapy, such as Cytokine Release Syndrome (CRS) and neurological Immune-cell associated neurotoxicity syndrome (ICANS) [28]
The first method of co-infusion of CAR T cells with checkpoint blockade Abs is being investigated in glioblastoma patients, where patients will be treated with a second generation epidermal growth factor receptor variant III (EGFRvIII)-directed CAR T cells with the co-administration of Pembrolizumab, a PD-1 monoclonal antibody checkpoint inhibitor (NCT03726515)
Summary
Cancer remains a main global challenge due to the lack of early diagnosis, the inherent biological complexity of the tumour microenvironment (TME) and the unavailability of highly efficacious treatment strategies. The concept of immunotherapy shifts the focus of “targeting” from tumour itself to a more personalised approach, where the host’s immune system is programmed to directly or indirectly attack cancer cells Several of these therapeutic strategies have been developed and approved for clinics, due to low treatment efficacy, drug resistance and tumour-induced immunosuppression, investigations are ongoing in the development of new adjuvant treatments and optimisation of existing immunotherapies, reviewed elsewhere [3,4]. In thisisreview, we provide attack cancer cells Several of these therapeutic strategies have been developed and approved for developments of selected immunotherapy strategies such as chimeric antigen receptor (CAR) T cell, clinics, due to low treatment efficacy, drug resistance and tumour-induced checkpoint inhibition, dendritic cell (DC)arevaccines, oncolyticofviruses (OV)treatments in both and haematological immunosuppression, investigations ongoing in and the development new adjuvant optimisation of existing immunotherapies, reviewed elsewhere [3,4].
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