CD44v6, STn & O-GD2: promising tumor associated antigens paving the way for new targeted cancer therapies

Front Immunol. 2023 Oct 3:14:1272681. doi: 10.3389/fimmu.2023.1272681. eCollection 2023.

Abstract

Targeted therapies are the state of the art in oncology today, and every year new Tumor-associated antigens (TAAs) are developed for preclinical research and clinical trials, but few of them really change the therapeutic scenario. Difficulties, either to find antigens that are solely expressed in tumors or the generation of good binders to these antigens, represent a major bottleneck. Specialized cellular mechanisms, such as differential splicing and glycosylation processes, are a good source of neo-antigen expression. Changes in these processes generate surface proteins that, instead of showing decreased or increased antigen expression driven by enhanced mRNA processing, are aberrant in nature and therefore more specific targets to elicit a precise anti-tumor therapy. Here, we present promising TAAs demonstrated to be potential targets for cancer monitoring, targeted therapy and the generation of new immunotherapy tools, such as recombinant antibodies and chimeric antigen receptor (CAR) T cell (CAR-T) or Chimeric Antigen Receptor-Engineered Natural Killer (CAR-NK) for specific tumor killing, in a wide variety of tumor types. Specifically, this review is a detailed update on TAAs CD44v6, STn and O-GD2, describing their origin as well as their current and potential use as disease biomarker and therapeutic target in a diversity of tumor types.

Keywords: CD44v6; Cancer; GD2; O-GD2; O-glycans; STn; Targeted Therapy; Tn.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, Neoplasm* / immunology
  • Humans
  • Immunotherapy
  • Neoplasms* / metabolism
  • Neoplasms* / therapy
  • Receptors, Chimeric Antigen*
  • T-Lymphocytes

Substances

  • Antigens, Neoplasm
  • Receptors, Chimeric Antigen
  • CD44 protein, human
  • Stn1 protein, human
  • CD44v6 antigen
  • sialogangliosides

Grants and funding

This study was cofounded by Instituto de Salud Carlos III (ISCIII) through the Project PI20/00813 to MD and co-funded by the European Union; European Regional Development Fund (FEDER) Grants from Science and Innovation (SAF2015-66015-R, and PID2019-110758RB-I00 to JMP), Instituto de Salud Carlos III (CIBERONC no. CB16/12/00228 to JMP; DTS20/00043; DTS22/00002 to MD), Project "FINANCED BY NEXTGENERATIONEU FUNDS, WHICH FINANCE THE ACTIONS OF THE RECOVERY AND RESILIENCE MECHANISM (MRR)". Funding entity: CARLOS III HEALTH INSTITUTE (ISCIII). ISCIII project code: AC22/00015 - Title: "Circulating tumor microenvironment components as predictors of response to immunotherapy in urothelial cancer" - PI: Marta Dueñas Porto. Project also funded by the Scientific Foundation of the Spanish Association Against Cancer (FCAECC) with project ID TRNSC213883DUEN, Transcan-3 JTC2022 and Fundación Eugenio Rodríguez Pascual (FERP-2022-79 to CR). IL is supported by a predoctoral fellowship from AECC (Spanish Ass. against Cancer), Predoctoral AECC 2019 grant number PRDMA19024LODE.