Recent advances in tumor associated carbohydrate antigen based chimeric antigen receptor T cells and bispecific antibodies for anti-cancer immunotherapy

Abstract

Tumor associated carbohydrate antigens (TACAs) are a class of attractive antigens for the development of anti-cancer immunotherapy. Besides monoclonal antibodies and vaccines, chimeric antigen receptor (CAR) T cells and bispecific antibodies (BsAbs) targeting TACA are exciting directions to harness the power of the immune system to fight cancer. In this review, we focus on two TACAs, i.e., the GD2 ganglioside and the mucin-1 (MUC1) protein. The latest advances in CAR T cells and bispecific antibodies targeting these two antigens are presented. The roles of co-stimulatory molecules, structures of the sequences for antigen binding, methods for CAR and antibody construction, as well as strategies to enhance solid tumor penetration and reduce T cell exhaustion and death are discussed. Furthermore, approaches to reduce "on target, off tumor" side effects are introduced. With further development, CAR T cells and BsAbs targeting GD2 and MUC1 can become powerful agents to effectively treat solid tumor.

Combined Action of Anti-MUC1 Monoclonal Antibody and Pyrazole-Platinum(II) Complexes Reveals Higher Effectiveness towards Apoptotic Response in Comparison with Monotherapy in AGS Gastric Cancer Cells

“…On many epithelial-origin cancer cells, MUC1 is enriched by specific tumor-associated carbohydrate antigens (TACAs), including Tn, T, sTn, and sT sugar structures. They are overexpressed on the surface of cancer cells compared to those on normal tissues [ 49 ]. It has been reported that the presence of such truncated glycan structures plays a key role in tumor initiation, progression, and metastasis as TACAs are able to interact with many factors participating in signaling pathways promoting cancer development (leading to the creation of a pro-tumor microenvironment, favoring tumor progression and metastasis) [ 50 ].…”

“…TACAs expression levels have been used as biomarkers of poor prognosis [ 51 ]. Moreover, they have been recently proposed as a specific “glycol-code” that could be considered as a novel immune checkpoint, offering new immunotherapeutic opportunities [ 49 , 50 ]. In our study, we assumed that anti-MUC1 based therapy could also block MUC1 associated TACAs expression.…”

The quest to develop an effective therapy for neuroblastoma

“…Although anti-GD2 monoclonal antibodies have been successful in treating patients with NB metastases in their bone marrow, this approach has not been beneficial as a single agent against patients with substantial and wide-spread disease (Sait & Modak, 2017). CAR T-cells have the potential for increased potency and durability compared with mAbs and it may in the future overcome this challenge to effective therapeutic outcomes in patients (Rashidijahanabad & Huang, 2020).…”

“…In addition, while antibodies generally do not penetrate the CNS (Rashidijahanabad & Huang, 2020), CAR-T cells can cross the blood-brain barrier (Iwasaki, 2017;Pule et al, 2008). Reverted NB of the CNS has emerged as a clinical entity since the adoption of anti-GD2 monoclonal antibodies, and CARs may provide an answer to this challenging clinical problem (Lammie et al, 1993;Sait & Modak, 2017).…”

Chimeric Antigen Receptor T-Cell Therapy: The Light of Day for Osteosarcoma

“…Disialoganglioside (GD2), an N-acetyl neuraminic acid-containing glycolipid antigen, is composed of five monosaccharides anchored to the lipid bilayer of the plasma membrane through a ceramide lipid [35]. GD2 expression is low in normal tissues [36] but high in solid tumors in children and adults, including neuroblastomas, Ewing's sarcoma, and OS [63].…”