Genetic engineering approaches to support clinical applications of T-cell receptor libraries targeting oncogenic mutations

T-cells targeting shared oncogenic mutations can induce durable tumor regression in epithelial cancer patients. Such T cells can be detected in tumor-infiltrating lymphocytes and peripheral blood of patients with the common metastatic epithelial cancers. In recent years, we and others have worked toward developing libraries of T-cell receptors targeting oncogenic mutations such as KRAS and TP53. Such T-cell receptor libraries offer an opportunity to treat patients with autologous or allogeneic T-cells genetically engineered to express selected T-cell receptors. Although attractive, such clinical application of T-cell receptor libraries should be accompanied by innovative genetic engineering platforms allowing cheaper, faster, and more flexible manufacturing solutions. This talk will discuss the methods to isolate, clone, and validate T-cell receptors targeting oncogenic mutations, the therapeutic potential of such libraries, and the genetic engineering platforms currently used for clinical manufacturing. We will also address the genetic engineering tools needed to allow such an approach to become widely and commercially applicable.

Learning Objectives:

1. Discuss methods to isolate, clone, and validate T-cell receptors targeting oncogenic mutations.

2. Define the therapeutic potential of TCR libraries targeting oncogenic mutations.

3. Indicate the current and future genetic engineering platforms needed to support clinical applications using off-the-shelf TCR libraries.