2022 Undergraduate Summer Research Program Participant

Home Department: Undeclared
Mentor: Vittorio Sebastiano (Obstetrics & Gynecology - Reproductive Biology)

“Prevention or Reversal of CAR T Cell Exhaustion Using Lentiviral Delivery System”

Chimeric antigen receptor T cells (CAR T) are immune cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy, for example in cancer therapies. However, CAR T cells experience a state of exhaustion in which their efficiency and effectiveness decrease as they age. Nina is working to see how the overexpression of the Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) can either reverse or prevent CAR T exhaustion. Yamanaka factors are used to induce a state of pluripotency in cells that have already differentiated into specific cell types and have lost their pluripotent developmental potential, essentially reversing biological age. The Yamanaka factors will be delivered into cells using a lentiviral vector Tet-On inducible system. The Tet-On system allows for control over gene expression activation by doxycycline, which can be used to assess gene function. Throughout this long-term project Nina will be learning how to perform various lab techniques including PCR, cloning, transfection, western blot, microscopy, tissue culture, chIP-sequencing, transformation, and more to help create a new lentiviral system for delivering Yamanaka factors into CAR T cells and to understand how Yamanaka factors impact CAR T cell function.