Tuning the hydrophobic segment in a polymer adjuvant achieved 100% tumor-free survival in mice.

Tumor vaccines need to trigger both killer cells and antibodies to beat cancer and build long-lasting memory. Most vaccines favor only one of these immune responses. To fix this, scientists tested a vaccine helper molecule made of amino acids. They kept its positive-charge part the same but increased its water-repelling hydrophobic part across three different lengths. Making this section longer changed the vaccine particle size, surface charge, and stiffness. These physical changes helped immune scout cells swallow the vaccine, activate through a sensor called TLR4, and display tumor targets. In mice, the formulation with the longest water-repelling chain stimulated powerful killer T cells and antibody-producing B cells. In a lung tumor model, it slowed tumor growth by 97.81% and initially kept 100% of mice tumor-free. After two new tumor challenges, 54.55% of mice stayed tumor-free for 644 days. It also worked against CT26 tumors.

Why it matters

Cancer vaccines often fail because they activate only one part of the immune system. This work shows that by adjusting the water-repelling part of a polymer adjuvant, both T cells and B cells are strongly activated. In mice, this led to complete tumor elimination and long-term immunity, offering a design principle for more effective cancer vaccines.

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