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745 Immune cell profiling of advanced-stage solid tumors patients treated with an oncolytic adenovirus encoding for TNF-a and IL-2 (TILT-123)
  1. Dafne CA Quixabeira1,2,
  2. Santeri A Pakola2,3,
  3. James Clubb2,4,
  4. Lyna Haybout1,2,
  5. Elise Jirovec2,
  6. Tatiana Kudling2,
  7. Joao Santos1,2,
  8. Victor Cervera-Carrascon1,2,
  9. Katriina Peltola5,
  10. Tuomo Alanko6,
  11. Jorma Sormunen6,
  12. Riitta Korpisaari6,
  13. Marjut Jaakkola7,
  14. Juha Kononen6,
  15. Susanna Juteau8,
  16. Claudia Kistler1,
  17. Suvi Sorsa1,2,
  18. Riikka Havunen1,2 and
  19. Akseli Hemminki1,2,3
  1. 1TILT Biotherapeutics Ltd, Helsinki, Finland
  2. 2Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
  3. 3Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland
  4. 4TILT Biotherapeutics, Helsinki, Finland
  5. 5Comprehensive Cancer Centre, Helsinki, Finland
  6. 6Docrates Cancer Center, Helsinki, Finland
  7. 7HUS, Helsinki University Hospital, Helsinki, Finland
  8. 8Helsinki University Hospital, Helsinki, Finland
  • 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.

Abstract

Background Development of immunotherapeutic treatment strategies for cancer treatment represents a relevant turning point for current cancer care. Durable responses and curative cases are some of the attractiveness that therapies such as immune checkpoint inhibitors and adoptive cell therapies elicit in responders. While most of the therapeutic benefits of checkpoint inhibitors are observed in patients bearing immune-infiltrated tumors, stimulating efficient anti-tumor response in poorly immune-infiltrated tumors is yet a challenge for currently approved immunotherapeutic drugs. In this context, emerging immunotherapies, such as oncolytic viruses that have the potential to overcome tumor immunosuppression and stimulate immune cells’ response, constitute promising therapeutic candidates. In the present work, a genetically modified oncolytic adenovirus expressing TNFa and IL-2 cytokines (Ad5/3-E2F-D24-hTNFa-IRES-hIL2), a.k.a. TILT-123, is being tested in phase I clinical trial as a monotherapy for the treatment of advanced-stage human solid tumors. TILT-123 has shown potent efficacy in a series of pre-clinical in vivo studies as a monotherapy and as an enabler of clinically used immunotherapies such as checkpoint inhibitors and several cell therapies.

Methods Tumor biopsies and peripheral blood of patients enrolled in an open-label Phase I clinical study using TILT-123 monotherapy treatment (TUNIMO, NCT04695327), were collected at screening and after TILT-123 administration. Tumor specimens were processed and embedded in paraffin blocks. Tumor slide sections were stained for multiplex immunohistochemistry analysis of intratumoral lymphocyte population changes upon TILT-123 treatment were quantified. Additionally, adenovirus intratumoral biodistribution was studied through the detection of E1a and hexon proteins. Peripheral blood mononuclear cells (PBMCs) were isolated and immune cell profiling was studied by flow cytometry.

Results Analyses show that TILT-123 treatment induces changes in immune cell populations detected in tumors and in the peripheral blood of patients treated with TILT-123. A detailed immunological profile will be presented.

Conclusions Treatment with TILT-123 oncolytic adenovirus changes the profile of immune cells circulating systemically and locally infiltrating injected and non-injected tumor sites.

Acknowledgements We thank the clinical site collaborators, the patients and their families, and all the academic collaborators for their valuable contributions to the present study.

Trial Registration NCT04695327

Ethics Approval TUNIMO (TILT-T115): This study was approved by the Finnish National Committee on Medical Research Ethics (TUKIJA); approval number HUS/1804/2020.

http://creativecommons.org/licenses/by-nc/4.0/

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