Year: 2026
Type: conference-abstract
Abstract: Background Immunotherapy has transformed cancer care, yet most solid tumors still escape. They remain invisible, suppress immune attack, and resist even our most advanced treatments. We asked a different question: instead of trying harder to re-engineer the immune system, what if we could make the tumor impossible to ignore? We developed a synthetic immunotherapy strategy that forces tumors to display a viral antigen already recognized by the body’s immune memory, effectively turning immune history into an anticancer weapon.Methods Using murine solid tumor models, we first established immune memory to the SARS-CoV-2 spike protein through vaccination with BNT162b2. We then injected spike-encoding mRNA–lipid nanoparticles directly into tumors, driving cancer cells to produce the viral antigen. We evaluated tumor control, survival, immune remodeling within the tumor microenvironment, induction of broader antitumor immunity through epitope spreading, and therapeutic synergy with anti-PD-L1 checkpoint blockade.Results This approach converted the tumor into a synthetic target for pre-existing antiviral immunity. Once tagged, tumors that had previously resisted immune attack became inflamed, recognizable, and vulnerable. Redirected immune memory drove tumor cell killing, reshaped the tumor microenvironment from ‘cold’ to ‘hot,’ and unleashed a broader immune response as dying cancer cells released their own native antigens. This secondary wave of immunity extended beyond the engineered target, creating systemic antitumor effects. When combined with anti-PD-L1 therapy, the platform produced striking tumor regression in otherwise refractory models.Conclusions These findings introduce a new therapeutic paradigm: do not just strengthen the immune system—reprogram the tumor. By using mRNA technology to install a target the immune system already knows how to destroy, we can transform immune evasion into immune recognition. Because the antigen payload is modular, this strategy could be adapted to match existing immunity across populations, offering a scalable and potentially off-the-shelf alternative to personalized neoantigen discovery. This work points to a bold new frontier in cancer immunotherapy: not teaching the immune system what cancer is, but teaching cancer how to be seen.Ethics Approval Animal ethics approval was obtained.
Author: Jiandong Huang
Institution: University of Hong Kong
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225147797