====== Neoantigen Peptide Vaccines ======

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[[Neoantigen]] [[peptide]]s are derived from unique [[antigen]]s created by [[somatic mutation]]s in cancer cells. Neoantigen peptide vaccines are personalized for each patient, targeting specific mutations in their cancer cells.
Tumor-Associated Antigen (TAA) Peptide Vaccines: TAAs are proteins overexpressed or uniquely expressed in cancer cells. Peptide vaccines containing TAAs aim to stimulate an immune response against these cancer-specific proteins.
Infectious Disease Peptide Vaccines: Peptide vaccines can also target infectious diseases by including peptides derived from pathogens, such as viruses or bacteria, to trigger an immune response.
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[[Neoantigen]]s arise from somatic [[mutation]]s that differ from [[wild type]] [[antigen]]s and are specific to each individual [[patient]], which provide tumor specific targets for developing personalized [[cancer vaccine]]s. Decades of work has increasingly shown the potential of targeting neoantigens to generate effective clinical responses. Current [[clinical trial]]s using neoantigen targeting cancer vaccines, including in combination with [[checkpoint blockade]] monoclonal antibodies, have demonstrated potent [[T-cell]] responses against those neoantigens accompanied by antitumor effects in patients. Personalized neoantigen vaccines represent a potential new class of cancer [[immunotherapy]]
((Aldous AR, Dong JZ. Personalized neoantigen vaccines: A new approach to cancer
immunotherapy. Bioorg Med Chem. 2018 Jun 1;26(10):2842-2849. doi:
10.1016/j.bmc.2017.10.021. Epub 2017 Oct 19. Review. PubMed PMID: 29111369.
)).
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They are exempt from central tolerance, can generate robust [[immune response]]s and can function as [[bona fide]] antigens that facilitate tumour rejection. 

It is a truly [[personalized therapy]] because most neoantigens are derived from unique [[mutation]]s in each tumor [[genome]].

Keskin et al.,  demonstrated that a strategy that uses multi-[[epitope]], personalized neoantigen [[vaccination]], which has previously been tested in patients with high-risk [[melanoma]], is feasible for tumours such as [[glioblastoma]], which typically have a relatively low [[mutation]] load, and an immunologically 'cold' tumour microenvironment. 

They used personalized neoantigen-targeting vaccines to immunize patients newly diagnosed with [[glioblastoma]] following surgical [[resection]] and conventional [[radiotherapy]] in a [[phase 1]]/[[Phase 1 B randomized controlled trial]]. Patients who did not receive [[dexamethasone]]-a highly potent [[corticosteroid]] that is frequently prescribed to treat [[cerebral edema]] in patients with glioblastoma-generated circulating polyfunctional neoantigen-specific [[CD4]]+ and [[CD8]]+ T cell responses that were enriched in a memory phenotype and showed an increase in the number of tumour-infiltrating T cells. Using single-cell T cell receptor analysis, they provided [[evidence]] that neoantigen-specific T cells from the [[peripheral blood]] can migrate into an intracranial glioblastoma tumour. Neoantigen-targeting vaccines thus have the potential to favourably alter the immune milieu of glioblastoma
((Keskin DB, Anandappa AJ, Sun J, Tirosh I, Mathewson ND, Li S, Oliveira G,
Giobbie-Hurder A, Felt K, Gjini E, Shukla SA, Hu Z, Li L, Le PM, Allesøe RL,
Richman AR, Kowalczyk MS, Abdelrahman S, Geduldig JE, Charbonneau S, Pelton K,
Iorgulescu JB, Elagina L, Zhang W, Olive O, McCluskey C, Olsen LR, Stevens J,
Lane WJ, Salazar AM, Daley H, Wen PY, Chiocca EA, Harden M, Lennon NJ, Gabriel S,
Getz G, Lander ES, Regev A, Ritz J, Neuberg D, Rodig SJ, Ligon KL, Suvà ML,
Wucherpfennig KW, Hacohen N, Fritsch EF, Livak KJ, Ott PA, Wu CJ, Reardon DA.
Neoantigen vaccine generates intratumoral T cell responses in phase Ib
glioblastoma trial. Nature. 2018 Dec 19. doi: 10.1038/s41586-018-0792-9. [Epub
ahead of print] PubMed PMID: 30568305.
)).
===== References =====