Applications
Although our project is focused on enhancing immune recognition in cancer, the principle of engineering proteins to improve their stability and binding affinity can reach far beyond oncology. By strengthening the way MHC molecules (and other proteins) interact with their ligands, we unlock possibilities in medicine, agriculture, and industry. Below, we describe three major potential applications of our work in greater detail, along with the responsibilities that come with them.
1. Enhanced Cancer Therapy
Cancer continues to be one of the greatest global health challenges, responsible for nearly 10 million deaths annually. While treatments like chemotherapy and radiation remain widely used, they often damage healthy tissue alongside cancer cells. Immunotherapies were developed to overcome this problem, by leveraging the body's own immune system to precisely attack tumors. However, even these advanced methods often fail when tumor antigens are poorly displayed to T-cells.
Our approach addresses this central bottleneck. By engineering MHC Class I molecules with improved stability and binding capacity for tumor-specific peptides, we aim to make cancer cells far more "visible" to immune surveillance. Stronger antigen presentation ensures that cytotoxic T-cells recognize cancerous cells more quickly and respond with greater efficiency. This improvement could enhance checkpoint inhibitors (such as PD-1 or CTLA-4 antibodies) by ensuring that once the "brakes" on T-cells are lifted, there are more clearly presented targets to attack. Similarly, adoptive T-cell therapies such as CAR-T or TCR-T could work better if tumor recognition is facilitated at the earliest step of antigen presentation.
Importantly, this approach could be especially beneficial for solid tumors, which often resist immunotherapies more than blood cancers. Solid tumors frequently escape by downregulating MHC or presenting weakly binding peptides. By directly modifying MHC molecules to present these peptides more effectively, our project aims to solve a problem at the root of tumor immune evasion. In this way, engineered MHC variants could become a universal enhancer for multiple existing and future immunotherapies, making treatments more reliable and potentially expanding the group of patients who can benefit.
2. Therapeutics Beyond Cancer
While our work is motivated by cancer treatment, the concept of stabilizing antigen presentation or protein--ligand binding has broader medical implications. Many diseases, including viral infections, autoimmune disorders, and degenerative conditions, are influenced by how the immune system recognizes (or fails to recognize) abnormal peptides. By extending the same engineering principles to these cases, we could design molecules that make harmful peptides easier to detect --- or conversely, reduce presentation of self-peptides that mistakenly trigger autoimmunity.
Image source: Envato Elements
For example, in viral diseases such as HIV or hepatitis, pathogens frequently evade detection by mutating peptides so that they no longer bind strongly to MHC molecules. Engineering MHC variants to stabilize these viral peptides could help the immune system recognize infected cells earlier and slow disease progression. Similarly, in autoimmune diseases where the immune system overreacts, engineered MHC variants could be used as research tools to study how altered presentation influences T-cell activation, leading to better therapeutic interventions.
Beyond immunology, our engineering approach can apply to other therapeutic proteins. The workflow of computational design, bacterial expression, and iterative testing is not restricted to MHC. It can also be adapted to enzymes used in drug delivery, proteins designed to cross biological barriers (such as the blood--brain barrier), or artificial receptors created to sense and respond to disease markers. In this way, our project demonstrates not just a single cancer-related application, but a general strategy for developing novel biologics across medicine.
3. Applications in Agriculture and Industry
The same engineering principles can also be applied outside of medicine. Agriculture, in particular, could benefit from more robust immune-like systems in plants. Plants rely on receptor proteins to recognize pathogens and trigger defenses, but these receptors are often limited in the range or strength of molecules they can bind. By applying our methods to engineer plant receptors, it may be possible to expand their recognition spectrum or improve their binding stability. This could create crops that are naturally more resistant to fungi, bacteria, or viruses, reducing the need for pesticides and leading to more sustainable farming. For example, engineering stronger immune receptors in staple crops such as rice, wheat, or corn could have significant global impact on food security.
Image source: Envato Elements
Industry also presents exciting opportunities. Many manufacturing processes rely on enzymes as catalysts. While natural enzymes are efficient, they often lack the stability needed to function in industrial conditions such as high temperatures, extreme pH, or the presence of solvents. Our workflow could be applied to redesign enzyme binding sites, making them more stable and adaptable. This could accelerate progress in biofuel production by creating enzymes that break down biomass more efficiently, or in food processing by developing enzymes that function under broader conditions. A recent study published in Nature (2025) described progress in designing efficient artificial catalysts --- an area that could directly benefit from our protein engineering framework.
Thus, while the immediate impact of our project lies in medicine, the broader vision is to provide a generalizable engineering platform for optimizing proteins wherever stability and binding are essential.
Risks and Considerations
We are aware that with these opportunities come serious responsibilities. Engineering immune proteins carries inherent risks. Increasing the binding affinity of MHC molecules may inadvertently cause autoimmunity, where T-cells attack healthy tissues. There are also dual-use concerns: theoretically, engineered MHC variants could be misapplied to help pathogens avoid immune recognition. Furthermore, in agricultural or industrial contexts, engineered proteins must be carefully tested to avoid unintended ecological effects.
To minimize these risks, our work has been conducted entirely in vitro, using bacterial expression systems and synthetic peptides only. No human cells or animal testing were involved. Moving forward, we believe it is critical to involve bioethics experts, regulatory authorities, and the public in evaluating how such technologies should be applied. Our team views this not just as a scientific project, but as a responsibility to ensure that advances in protein engineering are safe, transparent, and aligned with societal benefit.
