Their latest studies, recently published in European Journal of Immunology and Nano Letters, researchers at NII reveal how fine-tuning tiny nanoparticles—engineered to mimic immune cells—can supercharge T cells, the body’s natural tumor killers, and significantly inhibit tumor growth.
Central to this advance is a clever application of nanotechnology to a basic rule of immunology: the way T cells detect and respond to threats.T-cells receives activation signal from professional antigen presenting cells. Subsequently, T cells recognize infected or cancerous cells via small fragments called antigenic peptide displayed on major histocompatibility complex (MHC) molecules. To mimic this process and control it outside the body, scientists created nanoscale artificial antigen-presenting cells (aAPCs)—tiny iron-oxide-based nanoparticles coated with tumor-specific peptide-MHC (p-MHC) and co-stimulatory molecules.
But here's the twist: it turns out that not just the presence, but the number—or “valency”—of these p-MHC molecules on these aAPCs is critical. The two studies systematically varied the number of p-MHCs per particle and found a threshold valency that could robustly activate T cells. These “high-valency” aAPCs led to greater T cell expansion, production of powerful tumor-killing proteins like granzyme B, and enhanced infiltration into tumors in mice. Tumor growth was suppressed, and survival benefit was enhanced.
One study focused on ex vivo (outside the body) expansion of tumor-specific T cells using high-valency aAPCs. These "trained" T cells were then reinfused into mice bearing aggressive melanomas, where they significantly curbed tumor growth and extended survival. The other study went a step further—testing whether these particles could work directly in vivo (inside the body). Indeed, high-valency aAPCs injected into tumor-bearing mice not only expanded adoptively transferred T cells but also rallied the body's own endogenous tumor-specific T cells, achieving meaningful tumor suppression.
These findings collectively highlight a subtle but powerful design principle in immunoengineering: geometry matters. Just like soldiers need clear signals and coordination, T cells need the right density and clustering of cues to respond effectively. The spatial configuration of these cues on nanoparticles—the “valency”—dictates whether a T cell remains dormant or turns into a cancer killer cell.
The implications are far-reaching. By fine-tuning nanoparticle surfaces, researchers can now build smarter, more potent immunotherapies that bypass the need for complex cellular manipulation or risky systemic drugs. This could streamline the production of T cell therapies, personalize cancer treatment, and ultimately bring the next generation of nanomedicine one step closer to the clinic.
As science zooms into the nanoscale, it seems that big breakthroughs are hiding in the smallest details.
References
Mondal A, Jamal F, Das A, Sahoo AK, Chaudhary K, Chowdhury S, Jha A, Singha S. Inhibition of Melanoma Growth by Ex Vivo Expanded Tumor-Specific CD8+ T Cells Is Dependent on the Configuration of Nanoscale Artificial APCs. Eur J Immunol. 2025 May;55(5):e202451676. doi: 10.1002/eji.202451676. PMID: 40440562.
Sahoo AK, Mondal A, Jamal F, Das A, Chaudhary K, Jha A, Bansal TS, Mandal P, Dhara AK, Yang Y, Singha S. Defining the Critical Valency of Peptide-MHC on Nanoscale Artificial Antigen Presenting Cells for Expanding Endogenous Tumor-Specific T-cells In Vivo. Nano Lett. 2025 Jul 9;25(27):10817-10825. doi: 10.1021/acs.nanolett.5c02012. Epub 2025 Jun 24. PMID: 40553438.
Written by Dr Banya Kar with inputs from Dr Santiswarup Singha and Arnab Sahoo