PD-L1-Targeting Lipid Nanoparticles
Northwestern researchers developed PD-L1-targeting lipid nanoparticles to directly neutralize or eliminate immunosuppressive cells in the tumor.
STING-Peptide Vaccine Fusion Protein
Researchers at MIT have developed a vaccine-vaccine adjuvant fusion protein that facilitates efficient trafficking of peptide vaccines to lymph nodes AND stimulates local immune cells to ensure robust immunological responses.
Featured on Bio2Bedside Episode #2 (starting at 3:57)
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The Opportunity
We’ve known for a while that activating STING has the potential to unleash a powerful anti-cancer immune response. STING signaling leads to secretion of type I interferons – immune-activating proteins that recruit T cells, mature dendritic cells, and help present tumor antigen. But while the idea has been around for a while, the execution has lagged.
Historically, small molecule STING agonists have struggled with poor specificity, short half-lives, and limited activity across STING gene variants in the population. So, the emergence of a good STING agonist would be a big deal, but thus far, it hasn’t happened.
The Invention
Well, instead of trying to stimulate STING with some type of therapeutic agonist, this platform cuts to the chase: just give the patient active, recombinant STING itself.
Hammond’s team at MIT engineered a slightly modified version of the STING protein that can self-assemble into active tetramers when incubated with its natural agonist, cGAMP. When delivered into mice with tumors, the recombinant STING construct induced strong type I interferon responses and a clear anti-tumor immune effect.
But, they didn’t stop there. The team fused the recombinant STING construct to a cancer-associated peptide, essentially turning it into a self-adjuvanting cancer vaccine: the STING provides innate immune activation, and the peptide gives the system something to respond to.
It’s simple, clever, and actually kind of elegant: deliver both signal (STING) and specificity (peptide) in one package, and let the immune system do its thing.
Differentiation & Potential Risk
- Mechanistically distinct: Doesn’t rely on small molecules—delivers the pathway directly.
- Clinically intuitive: STING is well-characterized; immune activation via IFN is a known win.
- Potential risk: Delivery, dosing, and systemic cytokine activation need to be managed carefully. Stability and intracellular delivery efficiency will need translational de-risking.
- Unique vector: Large protein construct offers lymph node homing and may preferentially activate dendritic cells.
Why This Matters Now
The field has been circling STING for years, but delivery and gene variant issues have made small molecule agonists hard to translate. This recombinant approach avoids many of those pitfalls and bundles antigen delivery + innate immune stimulation into one construct.
To me, this isn’t just one more therapeutic, it’s a clean reframing of how to use STING in cancer.
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Key Scientist
Key Publications
Published:
Self-assembled cGAMP-STINGΔTM signaling complex as a bioinspired platform for cGAMP delivery
Published: 21 April
STING Protein‐Based In Situ Vaccine Synergizes CD4+ T, CD8+ T, and NK Cells for Tumor Eradication
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