Generation of therapeutic T cell receptors for fibrolamellar cancer (SJ-19-0046)

St. Jude Reference #SJ-19-0046

Description

There is currently no cure for fibrolamellar hepatocellular carcinoma (FLC) and reported relapse rates vary between 57% and 100%. Because FLC is a systemic disease, it is very difficult to entirely surgically remove. Surgery is extremely aggressive, sometimes lasting up to 14 hours and often followed by necessary second-look surgeries since the tumor can metastasize throughout the body. Best current practices after aggressive surgical resection include long-term chemotherapy, which eventually fails to control tumor metastasis. In order to better treat these patients, researchers at St. Jude have created an isolated T cell receptor (TCR) with antigenic specificity for the fusion protein that is universally expressed in FLC cells.

This TCR can be used in TCR-T therapy for individuals who have the C12:03 HLA allele (and all of its sub-variants). In this case, T cells would be engineered to express this TCR and inserted into the patient to target the patient’s cancerous cells. This could be done alone or in conjunction with other therapies, including for example surgery, checkpoint blockade, and/or in conjunction with other genetic engineering in the transgenic T cells.

Keywords

Fibrolamellar hepatocellular carcinoma (FLC), T cell receptor (TCR), cancer, DNAJB1-PRKACA fusion protein, EIFDRYGEEV presented on the C*12:03 HLA molecule, JCC209_FLC_TIL4_clonotype4, CALDMFSGGYNKLIF, TRAV16*01, TRAJ4*01.

Granted patents or published applications

Pending US Patent application, and published as WO 2020/257575 A1 

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