Abstract 569P
Background
Ilixadencel, a cell-based allogeneic immune primer consisting of pro-inflammatory monocyte-derived dendritic cells (DCs) that are injected intratumorally (i.t) recently received Regenerative Medicine Advanced Therapy (RMAT) designation from FDA for the treatment of metastatic renal cancer (mRCC) when combined with the tyrosine kinase inhibitor sunitinb. The designation was based on the results from a randomized phase II trial (MERECA) in patients with synchronous mRCC. Sunitinib is known to block VEGF-dependent immunosuppression which potentially could explain the clinical signs of synergistic anti-tumour efficacy when sunitinib was combined with ilixadencel. Here we present preclinical data in the CT-26 mouse tumour model where i.t injection of allogeneic mouse-ilixadencel was combined with different immunosuppression blockers, including anti-VEGF, anti-PD-1 and anti-CTLA-4.
Methods
Allogeneic BM-derived pro-inflammatory DCs (mouse-ilixdencel) were produced from C57BL/6 mice. Cryopreserved and subsequently thawed cells were injected i.t (2 doses) as monotherapy or in combination with anti-VEGF (4 doses), anti-PD-1 (4 doses) or anti-CTLA-4 (2 doses) given i.p. in Balb/C mice, starting treatment when CT-26 tumours reached an average size of 100 mm3.
Results
Monotherapy with mouse-ilixadencel, anti-PD-1 or anti-VEGF had no or only marginal effect on tumour growth while monotherapy with anti-CTLA-4 significantly delayed tumour growth without inducing any complete tumour responses. Mouse-ilixadencel in combination with anti-PD-1 or anti-VEGF trended to delayed tumour growth without inducing any complete responses. When ilixadencel was combined with anti-CTLA-4, 50-70% of the treated animals (data from 2 independent experiments) had a complete tumour response. Notably, animals with complete tumour response where protected from tumour growth upon subsequent tumour re-challenge.
Conclusions
Intratumoral administration of allogeneic pro-inflammatory DCs induce a synergistic anti-tumour response when combined with anti-CTLA-4, including complete responses and signs of systemic anti-tumour immune memory.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Immunicum AB.
Funding
Immunicum AB.
Disclosure
A. Karlsson-Parra: Full/Part-time employment: Immunucum AB. All other authors have declared no conflicts of interest.