TCR Repertoire Changes during TIL Expansion: Clonal Selection or Drifting?

Abstract

T-cell receptor β analysis can be exploited to monitor changes in the clonotypic composition of tumor-infiltrating lymphocyte (TIL) during ex vivo expansion in IL2. Oligoclonal TILs are often outgrown by infrequent clonotypes with greater proliferative capacity, and this could impact the antitumor reactivity of the expanded TILs. See related article by Poschke et al., p. 4289

CD4+tumor-infiltrating lymphocytes secreting T cell-engagers induce regression of autologous patient-derived non-small cell lung cancer xenografts

“…Here, we describe the first ACT strategy using TIL secreting TCE (TIL STAb ) and demonstrate their enhanced therapeutic activity over standard TIL in mice bearing established autologous NSCLC tumors. Furthermore, even after the loss of tumor-dominant TCR clonotypes and overgrowth of T cell clones that were marginally detectable in primary tumors during the ex vivo TIL expansion (25), we were capable of redirecting only TIL STAb against EGFR tumor cells in vitro and in vivo .…”

The Identification and Clinical Applications of Mutated Antigens in the Era of Immunotherapy

“…Similarly, from the identification of gene mutations and neoantigens to the validation and production of the neoantigen-based treatment, the cost of personalized neoantigen treatment can be very expensive [ 7 , 36 ]. One strategy for cost reduction may include the development of vaccines targeted at shared neoantigens; this would also potentially significantly increase access of neoantigen vaccines to an appropriately applicable population [ 29 , 37 , 51 ]. Another strategy to reduce cost is the development of combination therapies of traditional immunotherapy drugs with neoantigen based therapies [ 7 , 36 ].…”