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Neoantigens in Hematologic Malignancies.

Melinda A Biernacki1,2, Marie Bleakley1,3

  • 1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.

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|March 3, 2020
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Summary
This summary is machine-generated.

Cancer neoantigens, derived from aberrant proteins, are promising targets for T cell immunotherapies. Despite fewer mutations in blood cancers, neoantigens are identified across various hematologic malignancies, showing therapeutic potential.

Keywords:
T cell receptorfusion proteinshematologic malignancieshuman leukocyte antigenimmunotherapymutationsneoantigen

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Area of Science:

  • Immunology
  • Oncology
  • Genetics

Background:

  • T cell cancer neoantigens are peptides from aberrant proteins (mutated, fusion) presented with human leukocyte antigens on cancer cells.
  • Neoantigen-specific immunotherapies aim to avoid "on-target, off-tumor" toxicity due to exclusive expression on malignant cells.
  • Prior successes with neoantigen vaccines (melanoma, glioblastoma) and T cell therapies in solid tumors validate neoantigens as therapeutic targets.

Purpose of the Study:

  • To review advances in neoantigen discovery.
  • To describe the spectrum of identified neoantigens in hematologic malignancies.
  • To discuss the clinical translation potential of these neoantigens.

Main Methods:

  • Review of advancements in sequencing technology for antigen discovery.
  • Analysis of identified neoantigens across diverse hematologic malignancies.
  • Evaluation of clinical translation strategies for neoantigen-based therapies.

Main Results:

  • Neoantigens are derived from mutated and fusion proteins specific to cancer cells.
  • Hematologic malignancies, despite fewer mutations than solid tumors, harbor identified neoantigens.
  • Examples include mutated NPM1, PML-RARA (AML), ETV6-RUNX1 (ALL), BCR-ABL1 (CML), and immunoglobulins (lymphomas).

Conclusions:

  • Neoantigens represent valid and specific targets for cancer immunotherapy.
  • Advances in discovery technologies facilitate neoantigen identification in hematologic malignancies.
  • Clinical translation of neoantigen-based therapies holds significant promise for treating blood cancers.