125P - Enhancing the efficacy of neoantigen tumor vaccines in melanoma treatment through different administration times

Background

Immunotherapy is vital for melanoma treatment, with tumor vaccines showing promise. Previous studies suggest circadian rhythms may impact immune responses, yet their effect on tumor vaccine efficacy is unclear. To optimize vaccine outcomes, we investigated the differences in melanoma treatment efficacy when vaccines were administered at different times, aiming to find the optimal therapeutic window.

Methods

We compared the efficacy of a neoantigen tumor vaccine developed by our team when administered during the active phase (ZT21) versus the rest phase (ZT9) in C57BL/6 mice with B16-F10 melanoma (ZT refers to Zeitgeber Time, where ZT0 is the time of lights on, and ZT12 is lights off). IVIS imaging was used to track vaccine targeting of lymph nodes at different time points. Flow cytometry, immunohistochemistry, and RT-PCR were performed to assess changes in CD8+ and CD4+ T cells in the tumor microenvironment, lymph nodes, and spleen post-vaccination.

Results

In a melanoma model, vaccine administration during the rest phase (ZT9) showed better tumor inhibition compared to the active phase (ZT21). IVIS results indicated faster lymph node targeting at ZT9. Flow cytometry and immunohistochemistry revealed that ZT9 administration increased tumor-infiltrating CD8+ and CD4+ T cells, with a higher proportion of CD69+ T cells, leading to stronger anti-tumor immune responses.

Conclusions

Administering tumor vaccines during the rest phase, compared to the active phase, leads to faster lymph node targeting and stronger anti-tumor immune responses, resulting in better therapeutic outcomes. Thus, treatment timing should be considered in clinical immunotherapy, with vaccines administered during the rest phase for maximum clinical benefit.

Legal entity responsible for the study

West China Hospital, Sichuan University.

Funding

Sichuan Science and Technology Program.

Disclosure

All authors have declared no conflicts of interest.