51P - Delivering complete responses against solid tumors by checkpoint blockade enabled with tumor necrosis factor alpha and interleukin-2 armed adenovir...

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Neuroendocrine Cancers
Presenter Victor Cervera-Carrascon
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors V. Cervera-Carrascon1, J.M. Santos1, M. Siurala2, R. Havunen1, S. Sorsa2, A. Hemminki1
  • 1Oncology, University of Helsinki-Faculty of medicine, 0014 - Helsinki/FI
  • 2Tilt, TILT Biotherapeutics Ltd, 00290 - Helsinki/FI



Immune checkpoint inhibitors have been delivering promising results in an increasing number of indications. This approach proved the potential benefits of the use of the immune system as a tool against malignant cells. However, there is still room from improvement as there is a considerable number of patients not benefiting from these therapies. One of the biggest obstacles to overcome for those unresponsive patients is the lack of immune presence in the tumor. To overcome that limitation, we hypothesize that viruses are an appealing tool, as they are inherently able to attract the attention of the immune system and to express different transgenes. In our case, the viruses were armed with tumor necrosis factor alpha (TNFα) and interleukin-2 (IL-2), two cytokines to improve the trafficking to the tumor and enable T-cell mediated responses in the tumor.


To study the previously described scenario, an in vivo model of subcutaneous melanoma (B16.OVA) was used. Three different experiments were carried out (n = 48, 75 and 94) in order to assess the benefits and to understand the effect in the tumor microenvironment after the treatments.


When both therapies where given together, they delivered significantly better results than single treatment groups in term of overall survival and tumor growth control. From all the tested conditions, the treatments delivered better results when virotherapy was initiated before checkpoint blockade, in a “prime and boost” approach. In this set up, a 100% complete response was achieved (HR = 0.026 [0,005; 0,139] when compared with checkpoint blockade alone and HR = 0.069 [0,015; 0,327] when compared with virotherapy alone). The biological samples obtained through the study revealed a shift towards a Th1 cytokine status in the tumor while profile of the immune cell population also showed a significant change towards to the antitumor subsets.


The purpose of this study was to try to overcome poor immune infiltration in order to enable checkpoint blockade therapies, based on the results, the objectives were achieved after the use of a viral platform delivering immunostimulatory cytokines in the tumor that helped to redesign the tumor microenvironment.

Clinical trial identification

Legal entity responsible for the study

Cancer Gene Therapy Group


TILT Biotherapeutics Ltd.


V. Cervera-Carrascon, J.M. Santos, M. Siurala, R. Havunen and S. Sorsa: Employee of TILT Biotherapeutics. A. Hemminki: Shareholder in Targovax ASA (Oslo, Norway) and in TILT Biotherapeutics Ltd. (Helsinki, Finland). Employee of TILT Biotherapeutics.