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815 Combination with IL-15Rβγ superagonist, Nanrilkefusp alfa, enhances CAR T and BOXR T cell anti-tumor activity
  1. Emily Kuiper1,
  2. Kathleen Whiteman2,
  3. Daniel Garafola1,
  4. Pratirodh Koirala1,
  5. Shannon Smith1,
  6. Klara Danova3,
  7. Ekaterina Simonova3,
  8. Lenka Palova Jelinkova3,4,
  9. Irena Adkins3,4 and
  10. Amy Jensen-Smith1
  1. 1Sotio Biotech Inc., Cambridge, MA, USA
  2. 2Unum Therapeutics, Cambridge, MA, USA
  3. 3Sotio Biotech a.s., Prague, Czech Republic
  4. 42nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Nanrilkefusp alfa (Nanril, SOT101) is an IL-15Rβγ superagonist that is comprised of the IL15 cytokine fused to the IL-15Rα and has demonstrated a favorable safety profile and encouraging efficacy signals as a monotherapy and in combination with KEYTRUDA® (pembrolizumab) in the Phase 1/1b AURELIO-03 trial. SOTIO’s BOXR cell therapy platform is designed to improve the functionality of CAR-T cells by incorporating novel transgenes that are co-expressed with tumor-targeting receptors to overcome resistance and improve the function of respective immune cells in the solid tumor microenvironment. Here we tested the combination of Nanril with CAR-T or BOXR-T cells in vitro and in in vivo efficacy studies.

Methods BOXR-T cells, CAR-T cells or untransduced (UTD) control T cells were treated with 0.1–1 nM Nanril for 3- 7 days and proliferation and memory phenotype were assessed by flow cytometry; RNAseq analysis was also performed. To assess in vitro cytotoxicity, T cells were pre-treated for three days with 0.1 nM Nanril and were then co-cultured with target cells and cell killing was monitored using Incucyte analysis. CAKI-1 and NCI-H1975 tumor models were used to assess CAR-T and BOXR-T cell anti-tumor activity in combination with Nanril where the Nanril dosing regimen was administered 7 days following CAR-T or BOXR-T cells treatment.

Results Nanril treatment induced proliferation in UTD, CAR-T and BOXR-T cells in a dose-dependent manner. Shifts in T cell memory populations were also observed with increasing Nanril concentration, resulting in a higher proportion of effector memory cells and subsequently improved in vitro cytotoxicity. RNAseq analysis findings were consistent with increased proliferation and differentiation with Nanril treatment. When tested in vivo, BOXR-T cells had superior anti-tumor activity compared to CAR-T cells and combination treatment with Nanril further improved both BOXR-T and CAR-T cell efficacy and increased peripheral blood expansion.

Conclusions These data demonstrate that combination of Nanril with BOXR-T and CAR-T cells results in improved T cell function and anti-tumor activity in preclinical models. Combination of Nanril with T cell-based therapies may be a promising approach to increase efficacy in difficult-to-treat solid tumors.

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