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Personal tumor antigens in blood malignancies: genomics-directed identification and targeting
Livius Penter, Catherine J. Wu
Livius Penter, Catherine J. Wu
Published January 27, 2020
Citation Information: J Clin Invest. 2020;130(4):1595-1607. https://doi.org/10.1172/JCI129209.
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Review Series

Personal tumor antigens in blood malignancies: genomics-directed identification and targeting

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Abstract

Hematological malignancies have long been at the forefront of the development of novel immune-based treatment strategies. The earliest successful efforts originated from the extensive body of work in the field of allogeneic hematopoietic stem cell transplantation. These efforts laid the foundation for the recent exciting era of cancer immunotherapy, which includes immune checkpoint blockade, personal neoantigen vaccines, and adoptive T cell transfer. At the heart of the specificity of these novel strategies is the recognition of target antigens presented by malignant cells to T cells. Here, we review the advances in systematic identification of minor histocompatibility antigens and neoantigens arising from personal somatic alterations or recurrent driver mutations. These exciting efforts pave the path for the implementation of personalized combinatorial cancer therapy.

Authors

Livius Penter, Catherine J. Wu

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Figure 2

Classes of personal antigen targets in blood malignancies.

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Classes of personal antigen targets in blood malignancies.
(A) Minor his...
(A) Minor histocompatibility antigens often arise due to SNPs, resulting in differing physiological protein variants between the donor and the host of allogeneic HSCT. Other mechanisms giving rise to mHAs, such as frameshift mutations, have also been described and are reviewed extensively elsewhere (183). (B and C) Somatic mutations (B) and gene fusions due to chromosomal aberrations (C) give rise to physiologically nonexistent, tumor-specific protein variants. (D) Aberrant posttranslational modifications add neoepitopes to physiological proteins. (E) Alternative splicing results in neojunctions due to altered posttranscriptional processes in tumor cells. (F) Hypervariable Ig regions can be immunogenic, disease-specific epitopes in B cell malignancies.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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