Advances in personalized cancer immunotherapy

Abstract

There are currently three major approaches to T cell-based cancer immunotherapy, namely, active vaccination, adoptive cell transfer therapy and immune checkpoint blockade. Recently, this latter approach has demonstrated remarkable clinical benefits, putting cancer immunotherapy under the spotlight. Better understanding of the dynamics of anti-tumor immune responses (the "Cancer-Immunity Cycle") is crucial for the further development of this form of treatment. Tumors employ multiple strategies to escape from anti-tumor immunity, some of which result from the selection of cancer cells with immunosuppressive activity by the process of cancer immunoediting. Apart from this selective process, anti-tumor immune responses can also be inhibited in multiple different ways which vary from patient to patient. This implies that cancer immunotherapy must be personalized to (1) identify the rate-limiting steps in any given patient, (2) identify and combine strategies to overcome these hurdles, and (3) proceed with the next round of the "Cancer-Immunity Cycle". Cancer cells have genetic alterations which can provide the immune system with targets by which to recognize and eradicate the tumor. Mutated proteins expressed exclusively in cancer cells and recognizable by the immune system are known as neoantigens. The development of next-generation sequencing technology has made it possible to determine the genetic landscape of human cancer and facilitated the utilization of genomic information to identify such candidate neoantigens in individual cancers. Future immunotherapies will need to be personalized in terms of the identification of both patient-specific immunosuppressive mechanisms and target neoantigens.

Tailoring Biomaterials for Cancer Immunotherapy: Emerging Trends and Future Outlook

“…[215] A deeper understanding of tumor immunology and antitumor immune responses is indispensable for further discoveries and innovations of cancer immunotherapy. [220] Recently, neoantigens, or antigens derived from an individual tumor's specific mutations, have been leveraged for personalized cancer immunotherapy. Much like chemotherapy and radiation, the off-target toxicity associated with cancer immunotherapy can be drastic in approaches including vaccines, cytokines, checkpoint blockades, and cell therapies.…”

“…Ideally, each individual tumor must be treated in a personalized manner. [220] Recently, neoantigens, or antigens derived from an individual tumor's specific mutations, have been leveraged for personalized cancer immunotherapy. [18,69,221] With the development of sequencing technology, researchers are able to know the genetic landscape of human cancers, as well as identify specific neoantigens in each individual patient.…”

Breast Cancer Neoantigens Can Induce CD8+ T-Cell Responses and Antitumor Immunity

“…Our sequencing and epitope prediction algorithms are similar to those of other investigators: we identified somatic missense mutations through exome sequencing of tumor and normal tissue, followed by expression analysis by RNA sequencing, as many mutations are not expressed. Our final step towards identification of candidate neoantigens involved the use of computer algorithms that predict which mutations can give rise to peptides that can be presented by the patient’s HLA alleles (30,35,36). Preclinical studies performed to date suggest that the majority of candidate neoantigens, i.e.…”

Immune checkpoint inhibitors‐induced neuromuscular toxicity: From pathogenesis to treatment

“…In the last few years, medical advances have led to the discovery and successful clinical implementation of several classes of immunotherapy against cancer, including vaccination, adoptive cell transfer, and immune checkpoint inhibitors (ICIs) . Several ICIs, including ipilimumab (an antibody targeting cytotoxic T lymphocyte associated antigen 4, CTLA‐4), nivolumab, pembrolizumab, and cemiplimab (antibodies directed against the programmed cell death 1, PD‐1), atezolizumab, durvalumab, and avelumab (anti‐PD‐1 ligand, PD‐L1), have led to improved survival in patients with various cancer types including lung, kidney, liver, bladder and breast cancer, melanoma and lymphomas .…”