Tumor-associated carbohydrate antigens and glycolipids (TACAs)

Cancer-associated glycans and lipids on tumor and leukemic stem cell surfaces represent a specialized class of cell-surface markers that are aberrantly expressed during oncogenesis [1, 5]. These molecules, which include tumor-associated carbohydrate antigens (TACAs) such as Tn, sialyl-Tn, and Lewis antigens, as well as glycolipids like gangliosides (e.g., GD2, GD3) and globosides (e.g., Globo H), are critical for the maintenance of the cancer stem cell (CSC) and leukemic stem cell (LSC) phenotypes [1, 4, 12]. They actively participate in biological processes such as self-renewal, immune evasion, and metastatic spread by modulating signal transduction and cell-matrix interactions [1, 8, 10]. Because CSCs and LSCs are often resistant to standard therapies and drive tumor relapse, these surface glycans and lipids have emerged as high-priority targets for immunotherapy [1, 2, 13]. Current therapeutic strategies include monoclonal antibodies, carbohydrate-based vaccines, and CAR-T cell therapies designed to selectively eliminate these resilient cell populations while sparing normal tissues [1, 4, 5]. However, challenges such as the low immunogenicity of carbohydrates and potential off-target toxicities, like the neuropathic pain associated with GD2 targeting, remain significant hurdles in clinical development [1, 4].

Other names

Cancer-associated glycans and lipids on tumor and leukemic stem cell surfacesTumor-associated carbohydrate antigensCancer stem cell surface glycansLeukemic stem cell surface glycansGangliosidesGlobosidesTumor-associated glycolipids

Monoclonal antibodies targeting these surface antigens induce cell death through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) [4, 5]. Carbohydrate-based vaccines stimulate the immune system to produce endogenous antibodies against these antigens [4, 8]. Chimeric antigen receptor (CAR) T-cell therapies redirect T-cells to recognize and kill cells expressing specific glycans or glycolipids [1, 5]. Additionally, blocking these molecules can disrupt cell-cell adhesion and pro-survival signaling pathways [4, 8].