Background: Metastatic cholangiocarcinoma (CC), a form of gastrointestinal cancer that originates from the bile ducts, cannot be cured by currently available therapies, and is associated with dismal prognosis. In a previous case report, adoptive transfer of autologous tumor infiltrating lymphocytes (TILs), the majority of which recognized a tumor-specific point mutation, led to a profound and durable cancer regression in a patient with metastatic CC. Thus, more effective treatment for patients with this disease may be developed by using TILs that target cancer-specific mutations, but also other genetic aberrations such as gene fusions. In this context, fusions that involve () and function as oncogenes in a subset of patients with intrahepatic CC (ICC) represent particularly attractive targets for adoptive cell therapy. However, no study to date has explored whether fusions can be recognized by patients' T cells.

Method: To address whether fusions can be recognized by patients' T cells, we tested TILs from four patients with fusion-positive ICC for recognition of peptides and minigenes that represented the breakpoint regions of these fusions, which were unique to each of the four patients.

Results: We found that CD4 TILs from one patient specifically recognized the breakpoint region of a unique fusion, and we isolated a T-cell receptor responsible for its recognition.

Conclusions: This finding suggests that fusion-reactive TILs can be isolated from some patients with metastatic ICC, and thus provides a rationale for future exploration of T cell-based therapy targeting fusions in patients with cancer. Furthermore, it augments the rationale for extending such efforts to other types of solid tumors hallmarked by oncogenic gene fusions.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10106037PMC
http://dx.doi.org/10.1136/jitc-2022-006303DOI Listing

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