Identifying neoantigens for use in immunotherapy

Abstract

This review focuses on the types of cancer antigens that can be recognised by the immune system and form due to alterations in the cancer genome, including cancer testis, overexpressed and neoantigens. Specifically, neoantigens can form when cancer cell-specific mutations occur that result in alterations of the protein from 'self'. This type of antigen can result in an immune response sufficient to clear tumour cells when activated. Furthermore, studies have reported that the likelihood of successful immunotherapeutic targeting of cancer by many different methods was reliant on immune response to neoantigens. The recent resurgence of interest in the immune response to tumour cells, in conjunction with technological advances, has resulted in a large increase in the predicted, identified and functionally confirmed neoantigens. This growth in identified neoantigen sequences has increased the contents of training sets for algorithms, which in turn improves the prediction of which genetic mutations may form neoantigens. Additionally, algorithms predicting how proteins will be processed into peptide epitopes by the proteasome and which peptides bind to the transporter complex are also improving with this research. Now that large screens of all the tumour-specific protein altering mutations are possible, the emerging data from assessment of the immunogenicity of neoantigens suggest that only a minority of variants will form targetable epitopes. The potential for immunotherapeutic targeting of neoantigens will therefore be greater in cancers with a higher frequency of protein altering somatic variants. There is considerable potential in the use of neoantigens to treat patients, either alone or in combination with other immunotherapies and with continued advancements, these potentials will be realised.

Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer

“…PAP); or (ii) overexpressed antigens: highly expressed proteins in tumours due to malignancy, but have a baseline expression in healthy tissue (e.g. Her2/neu) [11,12]. As such, the TAA selected for the vaccine is critical to ensure appropriate specificity and induction of T-cell activity against the antigen in tumours [13].…”

Immunosurveillance and Immunoediting of Lung Cancer: Current Perspectives and Challenges

“…Tumor antigens can be differentiated into five categories: (i) viral antigens; (ii) differentiation antigens; (iii) cancer-germline antigens; (iv) overexpressed antigens; and (v) neoantigens ( Figure 6) [60][61][62][63]. As antigens (i)-(iv) can be expressed in normal tissues as well as cancer tissues, these antigens are more likely to promote immunological tolerance and are less likely to bring about effective anti-tumor immune responses [64].…”

Inducing multiple antibodies to treat squamous cell esophageal carcinoma

“…They focused on the phenomenon wherein various cancer antigens and antibodies are increased in the blood when cancer immunotherapy is effective. However, neoantigens and cancer antigens are highly diverse (there are several hundred types), and there are large individual differences in terms of which antigens are expressed and which components are antigenic [9,10]. Although neoantigens and cancer antigens are expected to predict the effects of treatment, the occurrence of antibodies against neoantigens is considered as a cancer patient-specific event.…”