Figure 3 from Preclinical Characterization and Phase I Trial Results of a Bispecific Antibody Targeting PD-L1 and 4-1BB (GEN1046) in Patients with Advanced Refractory Solid Tumors

Abstract

<p>GEN1046 promotes TIL expansion from patient-derived tumor tissue. Tumor tissues resected from patients with NSCLC were cut into pieces of 1 to 2 mm<sup>3</sup> and cultured in the presence of IL2 (10–50 U/mL) and GEN1046 (or a GEN1046 surrogate comprising the PD-L1–specific Fab arm of GEN1046 and a nonhumanized variant of the 4-1BB–specific Fab arm or atezolizumab (0.2 µg/mL), or with IL2 only for 14–17 days. <b>A,</b> Cell numbers after expansion were determined by flow cytometry, and total TILs, CD8<sup>+</sup> T cells, CD4<sup>+</sup> T cells, and NK cells are shown for three patients. Tumor PD-L1 expression and 4-1BB expression by CD8<sup>+</sup> T cells in the specimen at baseline are indicated. <b>B,</b> TCR repertoire analysis was performed by <i>TRB</i> RNA sequencing of the expanded TILs and the tumor fragments. Cumulative frequency of shared clonotypes, the 20 most abundant clonotypes in the GEN1046 surrogate–treated cultures, is shown. <b>C,</b> TILs expanded as in <b>A</b> were restimulated with enzymatically digested autologous tumor (TC) in the presence or absence of an MHC I–blocking antibody. Expression of 4-1BB and intracellular expression of IFNγ and CD107a in CD8<sup>+</sup> T cells were analyzed by flow cytometry.</p>

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