TUMOR ANTIGEN TARGETING

Overview

Antigens are markers on cells that can be used to specifically target cells that express the marker and, specifically, tumor antigens are those present on cancer cells but not normal cells.1


  • The ideal tumor antigen would be a "tumor-specific antigen", which is one that is expressed solely by malignant cells, thereby providing a unique target that will lead to maximal tumor elimination with minimal off-target toxicity.1
  • However, tumor-specific antigens are rare, as most antigens that are expressed by malignant cells are also found in normal tissues, therefore the more accurate designation of these antigens is "tumor-associated antigens (TAA)", rather than tumor-specific.1
  • TAAs can be broadly categorized into three groups:1
    • Aberrantly expressed self-antigens
    • Mutated self-antigens
    • Tumor-specific antigens

BIOLOGY OF TUMOR ASSOCIATED ANTIGENS1

  • (A)TAAs originate in various cellular compartments, including the nucleus, granules, cell membrane and cytoplasm. However, in order for effective antigen presentation to occur, (B) the TAA must localize to cellular compartments that facilitate antigen presentation.1
    • The abnormal expression of TAA by malignant cells, either through overexpression or aberrant localization, can lead to preferential presentation of TAA-derived immunogenic epitopes on the target cell surface.1

Therapeutic Potential1

  • A feature that makes a TAA ideal for immunotherapy is the dependency of the malignant cells on the expression of the TAA.
  • Targeting TAAs that drive the proliferation of the malignant clone will not only contribute to the reduction of the disease burden, but may eliminate the underlying malignant clone/stem cell, which must ultimately be eradicated for achieving cure.
  1. Alatrash G, Crain, A, et al. Chapter 7 – Tumor-Associated Antigens. Immune Biologic Allogeneic Hematopoeitic Stem cell Transplantation. 2019(2):107-125

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