ESMO- abstract:
440P - Intratumoral administration of pro-inflammatory allogeneic, “off-the-shelf”, dendritic cells in combination with anti-PD-1 or anti-CD137 has a synergistic anti-tumor effect
Presentation Number 440P Lecture Time 12:45 - 12:45
Speakers
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Alex Karlsson-Parra (Uppsala, SE)
Background
Activated NK-cells are known to play immune-regulatory “helper” functions, being able to recruit and activate “bystander” DCs and to promote cross-presentation of cell-associated antigens to CD8+ T cells by producing IFN-γ and TNF-α. We have recently shown that intratumoral administration of pro-inflammatory allogeneic mouse DCs (alloDCs) induce NK-cell recruitment and that human GMP-produced human alloDCs (ilixadencel) used in clinical trials (NCT00625755, NCT01974661, NCT02686944, NCT02432846), promote enhanced cytotoxicity and strong IFN-γ production in allogeneic NK-cells in vitro. Furthermore, co-culture of ilixadencel with allogeneic PBMCs leads to a pro-inflammatory environment inducing maturation and strongly enhanced cross-presentation in “bystander” DCs. Here we investigated the anti-tumor effect of intratumorally administered pro-inflammatory mouse alloDCs as monotherapy and in combination with anti-PD-1 or anti-CD137.
Methods
AlloDCs were produced from C57BL/6 mice and activated with a cocktail consisting of polyI:C, R848 and IFN-γ. After cryopreservation and subsequent thawing the cells were injected intratumorally 2 or 3 times starting at day 14 post subcutaneous CT-26 tumor cell inoculation in Balb/C mice. AlloDCs were given as monotherapy or in combination with anti-PD-1 or anti-CD137. The studies were conducted at Charles River Laboratories, Morrisville, NC, USA.
Results
AlloDCs did not significantly delay tumor progression, likewise did not anti-PD-1. Combined treatment with alloDCs/anti-PD-1 significantly delayed tumor progression, while treatment with intratumoral administrations of polyI:C combined with anti-PD-1 showed no significant delay. Anti-CD137 treatment significantly delayed tumor progression and also induced one complete (10%) tumor response. Notably, the combination of alloDCs with anti-CD137 induced a highly significant anti-tumor synergy, including complete tumor eradication in 3 out of 9 mice (33%).
Conclusions
Intratumoral administration of allogeneic pro-inflammatory DCs induces a synergistic anti-tumor response when combined with systemic anti-PD-1 or anti-CD137 treatment.