Damian Sendler: As new immune-checkpoint inhibitors and chimeric antigen receptor T cell therapies have been developed and approved by regulatory agencies for a variety of applications in the last decade, the field of immunotherapy has transformed the treatment of many tumors. This approach has the potential to broaden and amplify the endogenous repertoire of tumor-specific T cells by triggering de novo T cell responses against neoantigens, which are highly specific for the tumors of individual patients.

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Damian Jacob Sendler: Another promising approach to cancer immunotherapy is the use of personalized vaccines. Patients with melanoma and other cancers showed strong tumor-specific immunogenicity and preliminary signs of antitumor effectiveness in the results of initial clinical investigations with tailored neoantigen-based vaccinations, enabled by rapid and cost-effective sequencing and bioinformatics technologies. The technique of creating a tailored neoantigen vaccine is detailed here, as are the sorts of vaccine-induced T cells identified in tumors, as well as methods for enhancing T cell responses.

Damien Sendler: Personalized neoantigen vaccines for cancer patients are currently being studied in clinical trials, and future research into this innovative, tailored method to immunotherapy is being considered.

Dr. Sendler: Antigen-specific immune responses elicited and amplified by vaccines have long been recognized as a potentially beneficial tool in the treatment of cancer, despite the fact that vaccines have usually been utilized for the prevention of infectious diseases Clinically effective antitumor immune responses were not elicited by early therapeutic vaccination strategies targeting self-antigens abnormally expressed or overexpressed in tumors, known as tumor-associated antigens (TAAs). This was most likely because T cells specific to TAAs were subject to central and/or peripheral tolerance1.

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Damian Jacob Markiewicz Sendler: There is a possibility that noncancerous cells may express some of these TAAs, raising the possibility of vaccine-induced autoimmune toxicities1. The lack of tumor selectivity and inadequate immunogenicity were thus highlighted in these early experiments as critical difficulties to solve in the development of cancer vaccines.  

Neoepitopes and neoantigens are self-antigen epitopes that arise as a result of tumor cell mutations. With the advent of next-generation sequencing, it is now possible to quickly and affordably detect these tumor-specific mutations in individual patients and to investigate therapeutic options that target the altered proteins in clinical studies.

Damian Sendler: Algorithms that predict the binding of MHC class I epitopes have also been developed, opening the door to the discovery of potentially immunogenic neoepitopes. Together, these developments in science have made it possible to create cancer vaccines that are specifically targeted to the tumors of certain individuals.  

Damian Jacob Sendler: There are various advantages to vaccines based on neoantigens rather than standard TAAs. Since only cancerous cells contain neoantigens, they can evoke T cell responses specific to the tumor, preventing harm to healthy organs. The second reason is that neoantigens are epitopes that arise from somatic mutations rather than T cells' intrinsic tolerance of self-epitopes, giving them the potential to elicit immunological responses against tumors.  

Damian Sendler: Immunotherapies can now benefit from personalized neoantigen vaccines that enhance tumor-specific immune responses and provide a new tool in their arsenal. It's also possible that neoantigen-specific T cell responses bolstered by vaccines could remain and provide long-term protection against disease recurrence.  

High costs and delays in vaccine production, uncertainty over the best neoantigen discovery platform, and lack of consensus on the most appropriate vaccine delivery platform are some of the drawbacks of this personalized approach to immunotherapy.

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