1. Design, Synthesis, and Bioactivity Evaluation of a TF-Based Cancer Vaccine Candidate Using Lipid A Mimetics As a Built-In Adjuvant.
- Author
-
Gao L, Li G, Qiu C, Ye Y, Li X, Liao P, Ming W, Liu Z, Luo X, and Liao G
- Subjects
- Animals, Mice, Mice, Knockout, Humans, Female, Toll-Like Receptor 4 metabolism, Cell Line, Tumor, Lipid A analogs & derivatives, Lipid A chemistry, Lipid A pharmacology, Cancer Vaccines immunology, Cancer Vaccines pharmacology, Cancer Vaccines chemical synthesis, Mice, Inbred C57BL, Drug Design, Adjuvants, Immunologic pharmacology, Adjuvants, Immunologic chemical synthesis, Adjuvants, Immunologic chemistry
- Abstract
This study describes the design and synthesis of five TF-based cancer vaccine candidates using a lipid A mimetic as the carrier and a built-in adjuvant. All synthesized conjugates elicited robust and consistent TF-specific immune responses in mice without external adjuvants. Immunological studies subsequently conducted in wild-type and TLR4 knockout C57BL/6 mice demonstrated that the activation of TLR4 was the main reason that the synthesized lipid A mimetics increased the TF-specific immune responses. All antisera induced by these conjugates can specifically recognize, bind to, and induce the lysis of TF-positive cancer cells. Moreover, representative conjugates 2 and 3 could effectively reduce the growth of tumors and prolong the survival time of mice in vivo , and the efficacies were better than glycoprotein TF-CRM197 with alum adjuvant. Lipid A mimetics could therefore be a promising platform for the development of new carbohydrate-based vaccine carriers with self-adjuvanting properties for the treatment of cancer.
- Published
- 2024
- Full Text
- View/download PDF