5/ Decades of failure have informed today’s progress. Therapeutic vaccines may finally emerge as a core component of cancer care.
📖 Full review: rdcu.be/emkkd
@NeehaZaidi

@DrLizJaffee

4/ Many big questions remain: ideal platforms, personalized vs. off-the-shelf approaches, optimal combinations, and more. The next few years are critical, with multiple pivotal trials expected to report soon

3/ The new paradigm focuses on neoantigen vaccines in early-stage cancers, often in the adjuvant setting and combined with ICIs. Early clinical data in melanoma, PDAC, and more are promising—and point to therapeutic potential

2/ Earlier approaches—vaccines targeting overexpressed self-antigens as monotherapy in late-line disease—failed due to immune tolerance, weak immunogenicity, and exhaustion.
Clinically, it was akin to giving COVID vaccine to someone in the ICU with severe COVID

4/
Dr. Dan Shu and my commentary on this new paper is here: www.cell.com/immunity/ful...

3/
This new study takes things much further—showing that anti-VEGF + dual ICIs reprograms Tregs into a Th1-like fragile state in mouse CCA models and human tumors via an underappreciated pathway: anti-VEGF → TLS → BAFF/IL-12 → fragile Tregs

2/
It was wonderful to see this new study reproduce and extend key findings from our prior work on BAFF in cancer immunotherapy: 🔗 insight.jci.org/articles/vie...
BAFF (Cell Activating Factor) reprograms B cells to secrete IL12 and induces Treg "fragility"