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

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 1

Hematopoietic-restricted mHAs and tumor neoantigens.

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Hematopoietic-restricted mHAs and tumor neoantigens. (A) Differences in ...
(A) Differences in SNPs between donor and recipient that give rise to immunogenic epitopes are the basis of mHAs in the context of allogeneic HSCT. While mHAs with hematopoietic tissue restriction are targets for GvL effects, mHAs that are broadly expressed serve as basis for GvHD. (B) Identification of therapeutically relevant mHAs is based on epitope prediction of SNPs and selection of hematopoietically restricted candidates. (C) Tumor-specific neoantigens arise from somatic mutations in the tumor that are immunogenic. Neoantigens are only expressed by tumor cells and therefore are ideal targets for highly specific cellular therapeutic approaches. (D) Identification of neoantigens is based on epitope prediction of immunogenic mutations.