Bernard A. Fox, Co- founder, President, and CEO of UbiVac, shared Patrick Hwu’s, President and CEO at Moffitt Cancer Center, shared on LinkedIn:
“Cancer Vaccines 2026: Why now? What has changed, and what will it take to achieve cures?
It was a privilege to join Paolo A. Ascierto to open VAXON2026 our session on the emerging field of Dark Proteome cancer vaccines. Expect more at ESMO2026.
In framing remarks, we challenged participants to consider why cancer vaccines, after decades of disappointing clinical results, are now showing encouraging evidence of clinical benefit.
Several important developments are changing the landscape:
- Timing and disease burden matter. Vaccination in the adjuvant or minimal residual disease setting may be more effective than treating bulky, advanced cancers, where immunosuppressive mechanisms and immune dysfunction can limit therapeutic efficacy.
- Better vaccine platforms and adjuvants. Advances in mRNA/LNP technologies, innate immune activation, and antigen delivery are improving our ability to prime tumor-reactive T cells. Some earlier vaccine failures may have reflected inadequate adjuvants rather than inappropriate antigens.
- Combining vaccines with checkpoint blockade. Vaccines can generate tumor-reactive T cells, but those cells must overcome inhibitory pathways within the tumor microenvironment. The sequence and timing of combination therapies may prove critical.
- A dramatically expanded universe of tumor antigens. Beyond conventional tumor-associated antigens and mutation-derived neoantigens, the discovery of noncanonical proteins encoded by the dark genome is revealing previously unrecognized targets for immunotherapy.
- Measuring what really matters. Detecting vaccine-induced T cells in peripheral blood is not enough. We must establish whether those T cells recognize naturally presented tumor antigens, infiltrate tumors, and mediate tumor destruction.
Recent clinical results reinforce both the promise and the challenges. Personalized neoantigen vaccines are showing encouraging results in selected adjuvant settings, while success in advanced disease remains much less consistent.
The questions we posed:
- Why have some cancer vaccines succeeded where earlier approaches failed?
- Should we prioritize personalized neoantigens, shared tumor antigens, or both?
- Can immunopeptidomics and dark proteome discovery improve the identification of therapeutically relevant antigens?
- Are our vaccine and checkpoint inhibitor combinations optimally designed and sequenced?
- How do we distinguish vaccine immunogenicity from genuine tumor-destructive immunity?
- Can we overcome immune escape, antigen heterogeneity, and the immunosuppressive tumor microenvironment?
- How should we define success: tumor regression, prevention of recurrence, durable remission, or cure?
Our ultimate objective is not simply to generate immune responses. It is to generate immune responses that eliminate cancer and provide durable protection against recurrence.”
You can also read:
Cancer Vaccines Represent a Promising New Frontier in the Fight Against Cancer – PICI
