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293 Resultsof the first-in-human clinical trial with personalized multi-target adoptive cell therapy (ACTolog IMA101)
  1. Apostolia Tsimberidou1,
  2. Kerstin Guenther2,
  3. Amir Alpert3,
  4. Borje Andersson4,
  5. Zoe Coughlin3,
  6. Jens Fritsche2,
  7. Norbert Hilf2,
  8. Patrick Hwu4,
  9. Mamta Kalra3,
  10. Sabrina Kuttruff-Coqui3,
  11. Dominik Maurer2,
  12. Regina Mendrzyk2,
  13. Ali Mohamed3,
  14. Becky Norris4,
  15. Anna Nowak2,
  16. Rita Ort4,
  17. Carsten Reinhardt2,
  18. Fabian Richter2,
  19. Arun Satelli3,
  20. Oliver Schoor2,
  21. Kerry Sieger3,
  22. Harpreet Singh2,
  23. David Vining4,
  24. Claudia Wagner2,
  25. Toni Weinschenk2,
  26. Cassian Yee4 and
  27. Steffen Walter3
  1. 1MD Anderson Cancer Center, Houston, TX, USA
  2. 2Immatics Biotechnologies GmbH, Tuebingen, Germany
  3. 3Immatics US, Inc, Houston, TX, USA
  4. 4UT – MD Anderson Cancer Center, Houston, TX, USA


Background ACTolog (IMA101) is a personalized multi-target adoptive cell therapy (ACT) approach in which autologous T-cell products are redirected against multiple novel defined peptide-HLA (pHLA) cancer targets identified by the target discovery platform XPRESIDENT®. The primary endpoint was to assess the safety of ACTolog. Secondary endpoints were to assess the in vivo persistence of transferred T-cells and antitumor activity ( NCT02876510).

Methods HLA-A*02:01 positive patients with relapsed/refractory solid tumors whose tumor expressed ≥1 cancer target underwent leukapheresis and endogenous T-cells specific for up to 4 targets were primed and expanded in vitro. Patients received lymphodepletion (fludarabine 40 mg/m² and cyclophosphamide 500 mg/m² on days -6 to -3) followed by up to 4 × 1010 cells (day 0), and IL-2 (1 × 106 IU/m² SC twice daily, 14 days) (Cohort 1). In addition, cohort 2 received atezolizumab (1200 mg IV) every 21 days upon hematologic recovery. Infused T-cells were tracked in patients‘ blood via flow cytometry-based immunomonitoring as well as TCRβ sequencing. TCRs from target specific T-cells were identified from patients‘ T-cell products and characterized.

Results From 07/2017–03/2020, 214 patients were screened, and 14 heavily pre-treated patients with various tumor types were infused with 1–3 T-cell products each (table 1). The treatment was generally well tolerated. The most common adverse events observed to date were expected cytopenias, mostly attributed to the lymphodepleting regimen, and Grade 1–2 cytokine release syndrome. Prolonged disease stabilization was noted in three patients for 12 months, 12+ months, and 7 months. High frequencies of target-specific T-cells up to 78.7% of CD8+ cells were detected in the blood of treated patients, persisted for >1 year and were detected in post-treatment tumor biopsies. Characterization of individual TCRs contained in T-cell products showed a broad variation of TCR avidities with the majority of TCRs being of low avidity. High-avidity TCRs were identified from products of some patients, including a patient with 26% decrease in tumor measurements 6 weeks post-treatment. Tracking the respective T-cell clonotypes in patients‘ blood and tumor provides insights into the mechanism of tumor control. Six-month data will be presented at the conference.

Abstract 293 Table 1

Patient pre-treatment characteristics and response assessment

Conclusions This is the first reported trial demonstrating the feasibility and tolerability of a personalized ACT approach using multiple defined T-cell products directed to multiple precisely defined pHLA cancer targets. These results support further exploration of a multi-target ACT approach, particularly in the context of T-cells expressing high-avidity TCRs to such defined pHLA targets.

Trial Registration

Ethics Approval The study was approved by WCG WIRB, IRB tracking number 20162235. The study was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. All the study participants provided written informed consent before enrollment.

Consent Patient consent for publication is not required. Patients consented to participate in the study.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

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