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.

Technology Description

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.

Advantages

  • 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

Applications

  • Treating a wide array of tumor types
  • Screening antibody candidates for tumor antigen targeting drug development

Stage of Development

in vitro data

IP Status

Provisional patent application filed

Innovator

Jason Lohmueller, PhD