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Human germline-like monoclonal antibody against 5T4 enables potent ADC and CAR-T therapies for solid tumors

Yi-Qing Jiang1, Xiao-Jie Ma1, Yin-Man Wang2,3

  • 1Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS) and Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.

Acta Pharmacologica Sinica
|January 27, 2026
PubMed

Insights

Researchers developed novel antibody-drug conjugates and CAR-T cells targeting the 5T4 antigen. These therapies show potent cancer cell killing and tumor eradication, offering new hope for solid tumor treatment.

Area of Science:

  • Oncology
  • Immunotherapy
  • Biotechnology

Background:

  • 5T4 is an oncofetal antigen significantly overexpressed in various solid tumors.
  • Minimal 5T4 expression in normal adult tissues makes it an attractive therapeutic target.

Purpose of the Study:

  • To develop novel 5T4-targeted immunotherapies.
  • To evaluate the efficacy of antibody-drug conjugates (ADCs) and chimeric antigen receptor (CAR)-T cells based on a high-affinity antibody.

Main Methods:

  • Identification of germline-like human monoclonal antibodies against 5T4.
  • Construction and in vitro testing of m603-based ADCs with DM4 or MMAE payloads.
  • Development and in vitro/in vivo evaluation of m603-derived third-generation CAR-T cells (603z-CAR-T).

Main Results:

  • Antibody m603 demonstrated high affinity and potent binding to diverse cancer cell lines.
  • m603-based ADCs exhibited antigen-dependent cancer cell killing in vitro.
  • MMAE-conjugated ADC achieved durable tumor suppression in pancreatic cancer xenografts.
  • 603z-CAR-T cells effectively eradicated tumors and induced cytokine secretion (IFN-γ, IL-2).

Conclusions:

  • The germline-like antibody m603 serves as a versatile platform for 5T4-targeted therapies.
  • m603-based ADCs and CAR-T cells demonstrate significant potential for solid tumor immunotherapy.
  • This approach offers promising new avenues for treating various solid malignancies.
Keywords:
5T4antibody-drug conjugatechimeric antigen receptor T cellgermline-like monoclonal antibodypancreatic cancersolid tumors

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