A primer on recent developments in cancer immunotherapy, with a focus on neoantigen vaccines

Abstract

Cancer immunotherapy has now been conclusively shown to be capable of producing durable responses for a substantial number of patients. Adoptive cell transfer and checkpoint blockade therapies in particular both demonstrate that antigen-specific immune responses can be dramatically effective, even in previously refractory late stage disease. Such developments, together with advances in technology, have strongly encouraged revisiting the concept of neoantigen vaccines. Here we introduce basic ideas in the field to allow investigators from diverse backgrounds to understand these developments, grasp current issues, and contribute to further progress.

Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors in clinical trials for cancer immunotherapy

“…By reinstating the cancer-immunity cycle, cancer immunotherapy could strengthen the anti-tumor immune response, and restore the functions of the immune system to distinguish and eliminate tumor cells [ 5 ]. Currently, many immunotherapy therapies, including checkpoint inhibitors [ 6 ], monoclonal antibodies (mAbs) [ 7 ] and vaccines [ 8 ], are being developed for treating various cancers, especially melanoma, breast cancer and non-small cell lung cancer (NSCLC), etc. It has been widely recognized that combination of these novel therapies with standard chemo or radiotherapy could be an effective approach to overcome tumor-induced immunosuppression in clinic settings [ 9 – 11 ].…”

From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review)

“…The vast majority of these mutations occur in intracellular proteins. Therefore, such ‘neoantigens’ ( 44 ) are not readily recognized and targeted by antibodies. Fortunately, pMHC molecules and the system that transports these to the cell surface for T-cell recognition have developed during evolution, as aforementioned.…”

“…Taken together, there are various successful types of cancer immunotherapy. The design of currently popular T-cell-based immunotherapies has been described as follows ( 44 ):…”

“…With regards to cancer vaccines, a distinction exists between TAA vaccines and neo-epitope antigen vaccines. The strengths and weaknesses of the latter, and of future novel technologies, are described in a previous review ( 44 ).…”

In Silico Epitope Prediction Analyses Highlight the Potential for Distracting Antigen Immunodominance with Allogeneic Cancer Vaccines

“…When presented with thousands of foreign peptides, CD8 + T-cell responses are frequently directed toward a restricted group of or even a single antigen in a process known as immunodominance (45). While initially described in antiviral and antibacterial immune responses, this phenomenon and its implications are increasingly appreciated in vaccine administration (46,47). Given that shared tumor antigens are outnumbered by off-target antigens in allogeneic vaccines by two orders of magnitude, it is unlikely that the predominant vaccine-induced response will be beneficial.…”