Towards new horizons: characterization, classification and implications of the tumour antigenic repertoire

Haen, Sebastian P.; Löffler, Markus; Rammensee, Hans‐Georg; Brossart, Peter

doi:10.1038/s41571-020-0387-x

Cited by 153 publications

(108 citation statements)

References 164 publications

(230 reference statements)

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“…A major challenge in the design of T cell-based ACT strategies is to identify antigens expressed by tumor cells that could be targeted by adoptively transferred T cells. 10 Tumor antigens can be classified into two main groups: (a) tumor-specific antigens that are expressed exclusively on tumor cells (eg, neoantigens), and can arise from mutations, aberrant post-translational modifications, altered antigen processing or presentation, or other processes; (b) tumor-associated antigens that are expressed at low levels on normal tissues but are overexpressed on tumor cells. 10 The targeting of tumor-specific antigens by adoptively transferred T cells is expected to achieve the most specific and significant efficacy, but their elevated individual specificity reduces the clinical scope of this strategy.…”

Section: Tumor-s Pecific Effec Tor S For C An Cer Immunother Apie Smentioning

confidence: 99%

Beyond CAR T cells: Engineered Vγ9Vδ2 T cells to fight solid tumors

Rafia

Harly

Scotet

2020

Immunological Reviews

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Cancer, a general term used to describe a large group of life-threatening malignancies, represented the second leading cause of death in the world in 2018, according to the World Health Organization. Cancer cells can establish and develop in almost any organ or tissue of every individual. Solid tumors, which represent more than 90% of adult cancers, correspond to masses of cancer cells deeply enmeshed with tissues of origin (eg, lung, breast, prostate, colon, bladder). Liquid tumors such as lymphomas and leukemias develop in body fluids (eg, blood). Physiologically speaking, abnormal cells with somatic mutations and aberrant/dysregulated pathways grow uncontrollably, destroy adjacent tissues, and eventually spread into other organs. 1 Because of the difficulty to establish diagnosis at early stages, cancer eradication is very challenging. Standard treatments to cure cancer are based on chemotherapy or radiotherapy, but their poor specificity for cancer cells induces a substantial toxicity. Furthermore, because of inter-individual variability and tumor heterogeneity, the outcomes of these treatments are often unpredictable. A major recent advance of biomedical research is a better understanding of key roles played by the immune system in tumor surveillance, and the mechanisms developed by tumor cells to evade this surveillance and hack immune pathways to promote tumorigenesis. 2 Accordingly, novel strategies have emerged over the last decades that aim at enhancing, complementing, or restoring the ability of patient's immunity to generate specific and efficient responses,

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Section: Tumor-s Pecific Effec Tor S For C An Cer Immunother Apie Smentioning

confidence: 99%

Beyond CAR T cells: Engineered Vγ9Vδ2 T cells to fight solid tumors

Rafia

Harly

Scotet

2020

Immunological Reviews

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“…MS remains the only method that allows direct and definitive identification of the amino acid sequence of MAPs and TSAs [5,[27][28][29]. However, MS analyses require i) large tumor samples and ii) specialized equipment and expertise which are not widely available.…”

Section: Can Mtsas Be Identified Without Mass Spectrometry (Ms) Analymentioning

confidence: 99%

“…TAAs are MAPs which are not cancer-specific but are overexpressed in cancer cells (Table 1). Because they are part of the normal immune self, TAAs are not highly immunogenic and TAA vaccines have yielded disappointing results [5,6]. Strong evidence suggests that anti-tumor immune responses potentiated by ICT are directed against tumor-specific antigens (TSAs), that is MAPs found only on cancer cells [4,7,8].…”

Section: Introductionmentioning

confidence: 99%

The Origin and Immune Recognition of Tumor-Specific Antigens

Apavaloaei

Hardy

Thibault

et al. 2020

Preprint

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The dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predictions and reverse immunology studies cannot provide this type of conclusive evidence. Most TSAs are coded by unmutated non-canonical transcripts that arise from cancer-specific epigenetic and splicing aberrations. When searching for TSAs, mass spectrometry analyses must therefore interrogate not only the canonical reading frame of annotated exome but all reading frames of the entire translatome. The majority of aberrantly expressed TSAs (aeTSAs) derive from unstable short-lived proteins that are good substrates for direct MHC I presentation but poor substrates for cross-presentation. This is an important caveat because cancer cells are poor antigen-presenting cells and the immune system therefore depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs. We therefore postulate that, in the untreated host, most aeTSAs are undetected by the immune system. We present evidence suggesting that vaccines inducing direct aeTSA presentation by DCs represent an attractive strategy for cancer treatment.

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“…Was die angeführten Studien aber zumindest zeigen können, ist, dass sich das Konzept der individuellen Formulierung eines Arzneimittels als Tumorvakzine grundsätzlich bei Tumorerkrankungen umsetzen lässt [34]. Dafür mussten bereits wesentliche Herausforderungen bewältigt werden, beispielsweise mit maschinellem Lernen [32] oder anderen Ansätzen individuelle Zielstrukturen zu definieren, um ein Medikament nach entsprechenden Spezifikationen kurzfristig herzustellen und freigeben zu können.…”

Section: Individualisierte Vakzineunclassified

Individualisierte Immuntherapie von Tumorerkrankungen mittels Peptidimpfstoffen – Funktioniert das vielleicht doch?

Rammensee

Löffler

2020

Bundesgesundheitsbl

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Zusammenfassung Bereits der Arzt und Forscher Paul Ehrlich stellte die These auf, dass das Immunsystem nicht nur Infektionen bekämpft, sondern auch gegen Krebs vorgehen kann. Über die möglichen positiven Auswirkungen einer simultanen Infektion auf den Verlauf einer Krebserkrankung wurde bereits im alten Ägypten ca. 2600 v. Chr. berichtet. Jedoch wurde erst ab den 1960er-Jahren klar, dass das Immunsystem Krebszellen gezielt bekämpfen kann, und erst ab den 1990er-Jahren wurde langsam aufgeklärt, wie dies vor sich geht. Vor diesem Hintergrund sollen deshalb die Bemühungen der letzten 30 Jahre hinsichtlich der Entwicklung therapeutischer Impfungen gegen Krebserkrankungen kurz zusammengefasst und deren bisherige Erfolglosigkeit beleuchtet werden. Außerdem werden in einem Ausblick zukünftige eventuell Erfolg versprechende Entwicklungen in diesem Kontext diskutiert. Dabei werden die verfügbare wissenschaftliche Literatur, aber auch eigene Ergebnisse berücksichtigt. Es ergeben sich ganz zentrale Fragen, etwa: Wie unterscheiden sich Krebszellen von normalen Zellen? Wie kann das Immunsystem diese Unterschiede erkennen? Was sind tumorspezifische Antigene? Warum müssen tumorspezifische Antigene in individueller Weise ausgesucht und angewendet werden? Wie induziert man eine effiziente Immunantwort? Welche pharmazeutischen Formulierungen, Adjuvanzien und Impfrouten sind effektiv? Letztlich stellen wir dar, warum es sich möglicherweise doch lohnt, die bisher völlig erfolglose Peptidimpfung (gemessen an bisher zugelassenen Therapeutika) weiterzuverfolgen.

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Towards new horizons: characterization, classification and implications of the tumour antigenic repertoire

Cited by 153 publications

References 164 publications

Beyond CAR T cells: Engineered Vγ9Vδ2 T cells to fight solid tumors

Beyond CAR T cells: Engineered Vγ9Vδ2 T cells to fight solid tumors

The Origin and Immune Recognition of Tumor-Specific Antigens

Individualisierte Immuntherapie von Tumorerkrankungen mittels Peptidimpfstoffen – Funktioniert das vielleicht doch?

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