Ganglioside GM3 and Lipid A Mimetic Conjugate Combined with EcMPLA and QS-21 as a Potential Vaccine Candidate for Cutaneous Melanoma Immunotherapy

  • J Med Chem. 2026 May 14;69(9):11434-11447. doi: 10.1021/acs.jmedchem.6c00625.
Ruxin Liang  1 ,  Yifan Ye  1 ,  Haixin Liu  1 ,  Xiaohui Li  1 ,  Lingqiang Gao  1  2 ,  Hanyu Li  1 ,  Deying Yang  1  3 ,  Wenbo Ming  1 ,  Zhongqiu Liu  1  4 ,  Xiang Luo  1  4 ,  Guochao Liao  1
Affiliations
  • 1. Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
  • 2. School of Medicine Shaoxing Vocational & Technical College, Shaoxing 312000, China.
  • 3. Laboratory of Clinical Pharmacy, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China.
  • 4. Chinese Medicine Guangdong Laboratory, Zhuhai, Guangdong 519031, China.
PMID: 42077094 DOI: 10.1021/acs.jmedchem.6c00625
Abstract

Ganglioside GM3 is a well-established cutaneous melanoma-associated carbohydrate antigen. Efforts toward its clinical translation as a Cancer vaccine have been hampered by poor immunogenicity. This study describes the design and synthesis of a fully synthetic self-adjuvanting GM3-based conjugate vaccine (1) using lipid A mimetics as a carrier. Immunological evaluations demonstrated that conjugate 1 effectively elicited GM3-specific immune responses. The antisera induced by this conjugate recognized, bound to, and facilitated the destruction of GM3-positive Cancer cells. Combination with the adjuvants QS-21 and EcMPLA dramatically enhanced the immunogenicity and antitumor efficacy of conjugate 1 at a dose of 2 μg of GM3 per mouse. The IgG titers of 1/EcMPLA/QS-21 were more than twice those of GM3-KLH/Al. Furthermore, 1/EcMPLA/QS-21 conferred strong protection in tumor-challenge models, significantly delaying tumor growth and extending survival. These findings demonstrate the potential of conjugate 1 combined with EcMPLA and QS-21 as a candidate vaccine for melanoma immunotherapy.

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