Tumor-associated antigens - Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation - page 141

ch 7

Tumor-associated antigens

Gheath Alatrash, Jeffrey J Molldrem
Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD
Anderson Cancer Center, Houston, Texas, USA

Introduction

Tumor associated antigens (TAAs) have been effectively targeted in hema-
topoietic malignancies. Unlike minor histocompatibility antigens (mHiAs),
which are normal cellular proteins that can be immunogenic due to poly-
morphisms that cause amino acid differences between individuals, TAAs are
proteins that derive their immunogenicity due to their distinct expression
by tumor cells. Although TAAs are associated with a malignant cell pheno-
type, they can also be expressed by normal cells; however, the expression
of TAAs by the malignant cell has unique features that contribute to their
immunogenicity. This chapter will discuss TAAs in the setting of allogeneic
hematopoietic stem cell transplantation (allo-HSCT), focusing on their
biology and therapeutic potential.

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Biology of tumor-associated antigens

The ideal tumor antigen is one that is expressed solely by malignant cells,
thereby providing a unique target that will lead to maximal tumor elimina-
tion with minimal off-target toxicity. Although immunotherapy that targets
such antigens would be predicted to have minimal side effects, there is in
fact a paucity of immunogenic tumor-specific antigens (TSAs). Since most
antigens that are expressed by malignant cells are also found in normal tis-
sues, the more accurate designation of these antigens is tumor-associated,
rather than tumor-specific. TAAs are distinguished from normal cellular
proteins by distinct features in their levels of expression, localization or
major histocompatibility (MHC) processing, which allows for their effective
targeting in malignancies.

TAAs can be broadly categorized into three groups: aberrantly expressed
self-antigens, mutated self-antigens and TSAs ( Figure 7.1 ). Distinguish-
ing where an antigen falls within these categories is extremely important
in designing immunotherapies that preferentially target the tumor cells.
While mutated self-antigens, which oftentimes differ from their normal
counterparts by one or a few amino acids, may be effective targets for non-
immune-based therapies, such proteins may prove to be poor targets for