For the roughly 40 percent of Americans who will develop cancer at some point in their lives, chimeric antigen receptor T cells (CAR-Ts) offer an exciting new avenue for treatment. CAR-Ts work by targeting a tumor-specific antigen to selectively destroy cancer cells without harming normal tissue. Although CAR-Ts have enjoyed some success in clinical trials, cancer cells can drop the targeted antigen to evade lysis, necessitating the non-trivial process of designing and testing a new CAR-T. Also, persistent CAR-T activity can be toxic to healthy tissue. To avoid these issues, we created a universal CAR-T system that maintains a high binding affinity for tumor cells while also offering greater control over toxicity and more nimble design adaptability for treating a wide array of cancers.
With our system, patients would receive two treatments. The first involves a biotin-tagged antibody that binds to tumor cells. The second involves CAR-Ts that react with the tagged antibodies on the tumor cells. By separating the tumor-associated antigen from the CAR T cell, this system is much easier to adapt to changes in tumor antigen expression. Furthermore, it offers the potential for lower toxicity because the CAR T cell potency is directly controlled by the concentration of tagged antibody. Compared to other biotin-binding CARs, our engineered affinity-enhanced monomeric streptavidin 2(mSA2) biotin-binding protein domain hasa25-fold stronger affinity. When incubated together with target cells and various biotinylated tumor-specific antibodies, our adaptable mSA2-CARTs had comparable potency to traditional CARs.
- A single population of CAR T cells can target multiple tumor antigens
- Potential for reduced toxicity
- Anti-tumor efficacy on par with single-antigen CAR-Ts
- Can be used with the ever-increasing list of FDA-approved tumor-targeting antibodies
- Treating a wide array of tumor types
- Screening antibody candidates for tumor antigen targeting drug development
Stage of Development
Provisional patent application filed
Jason Lohmueller, PhD