Reimagining Immunity with Synthetic T-Cells: Revolutionary CRISPR-ALL Technology Redefines Immune Capabilities Against Incurable Diseases

Cancers and chronic infections like tuberculosis, malaria, and HIV have mastered the art of evasion, evolving around our immune defenses and the drugs developed against them. Dr. Theodore Roth has an ambitious plan to give the immune system a leg up against these incurable diseases, which have stumped modern medicine. “As a pathologist-scientist, I observe every day diseases where the natural set of immune cells is not able to resolve a patient’s disease. Current therapeutics largely move immune cells around these naturally evolved cell states. My objective is to see if new therapeutically useful human immune cell states can be created,” says Roth.

Combining immunology and bioengineering, Roth is reimagining the future of cell therapy. As a winner of the 2026 Michelson Prizes: Next Generation Grants, Roth will apply revolutionary genetic engineering tools to create synthetic immune cells with novel capabilities- capabilities never before seen in nature. “Our goal is to build new genes that give immune cells new functions specifically tailored to overcome cancer resistance mechanisms. If cancer can evolve new genes to evade the immune system, we want to give the immune system new genes to fight back,” he says. Ultimately, he will engineer “superhero” immune cells with new superpowers against cancerous and infectious supervillains.

Roth’s innovative approach stems from current engineering of CAR T-cells to target cancers, but is infinitely more powerful. Rather than targeting a single gene, he can genetically engineer thousands of genes at the same time to entirely reprogram cells for new functions. “I have spent 10 years developing ever more powerful tools to genetically manipulate human immune cells, progressing from knocking out one gene to now being able to insert tens of thousands of new DNA sequences into immune cells and test them simultaneously,” he says. 

Roth’s CRISPR-ALL technology elevates T-cell engineering from craftsmanship to industrial-scale innovation. He will mass-produce a collection of entirely novel, synthetic T-cells that may have a better chance against cancers and pathogens, specifically because these foes have never encountered them before. These diseases adapted to evade natural immune defenses, having spent centuries perfecting their strategies in a constant evolutionary battle. Faced with a new immune arsenal armed with new tactics against them, they will be rendered defenseless. 

For example, cancer cells have evolved to suppress immune responses that would otherwise eliminate them.  Roth says synthetic T-cells could outsmart the tumor at its own game by reprogramming immune cells to attack the cancer. “Macrophages and innate immune cells inside tumors are often tricked by cancer to become suppressive. We want to put new factors into T-cells that they can secrete to trick these cells back or block the cancer's suppressive mechanisms. We're exploring whether solutions need to be tumor-specific or could work broadly across cancer types,” he says. Another strength of the approach is that multiple functions can be programmed into a single T-cell, effectively arming it with a multitude of weapons that make it much harder or even impossible for the cancer to escape.

Roth is working with experts around the country to test the synthetic T-cells in various tumor and chronic infection models, as well as in clinical trials. This collaborative ecosystem accelerates the pathway to patients, turning scientific imagination into clinical reality at record speed. As co-founder and CSO of Arsenal Biosciences, earlier iterations of his technologies are already in clinical trials, paving the way for this new approach. “The Michelson Prize is providing our lab with support for the most ambitious research projects that we can imagine. This crucial early support for research at the forefront of what is technically possible, I truly believe, accelerates how quickly we're going to get curative immune cell medicines into patients,” says Roth.

While he is starting with cancer, Roth has no plans on stopping there. “We think that these genetic medicines are going to be a powerful class of therapies across many diseases. What we ultimately want it to do is to give immune cells the new functions they need to overcome any disease, whether to cure a cancer, halt autoimmune disease, or prevent neurodegeneration.” Therein lies the powerful nature of Roth’s revolutionary technology; it can be deployed against very different clinical problems to generate therapeutic T-cells fit for the job. The possibilities are limitless, and Roth is enthusiastic to explore them all.  “The exciting part is that our knowledge and technical capacity continuously expand. That means that every year we are more likely to crack open some new area of therapy that we've never been able to before.”

This is the kind of breakthrough science the Michelson Prize: Next Generation Grants was created to champion—outside-the-box ideas and inventive technologies with the potential to open new realms of discovery and redefine medical capabilities, with impact across disease areas. Roth acknowledges he is reaching for the moon, but also that in doing so, you never know what you might find along the way. “That's one of the beautiful things about science, if you're open to unexpected things. Sometimes you try to discover one thing, and it turns out you solved a different problem. That is one of the strongest arguments for curiosity-driven, ambitious science.”