Guided tumor ablation and targeted delivery of innate immune checkpoints to enhance cancer immunotherapy

This data repository contains data from PhD research acquired during the period between November 2019 and September 2024. This repository contains all quantitative data pertaining to the published papers from this thesis. In situ tumor ablation releases a unique repertoire of antigens from a heterogeneous population of tumor cells. High-intensity focused ultrasound (HIFU) is a completely noninvasive ablation therapy that can be used to ablate tumors either by heating (thermal (T)-HIFU) or by mechanical disruption (mechanical (M)-HIFU). How different HIFU ablation techniques compare with respect to their antigen release profile, their activation of responder T cells, and their ability to synergize with immune stimuli remains to be elucidated. Here, we compare the immunomodulatory effects of T-HIFU and M-HIFU ablation with or without the TLR9 agonist CpG in the ovalbumin-expressing EG7 tumor model. This data repository contains flowcytometry data characterizing the various immune cell populations in lymph nodes from mice with HIFU treated tumors. Furthermore, data to assess the ability of splenocytes from mice with HIFU treated tumors to activate CD8 T-cells ex-vivo is avialable. Lastly, data quantifying the presenece of inhibitory cytokines from western blot data is avialable. Neuroblastoma (NB) is a childhood malignancy characterized by overexpression of disialoganglioside GD2. Treatment with anti-GD2 monoclonal antibodies (aGD2 mAbs) has prolonged the survival of NB patients, however, long-term efficacy needs further improvement. NB tumor cells upregulate expression of the innate immune checkpoint and don’t eat me signal CD47 to evade immune recognition and phagocytosis by Signal regulatory protein alpha (SIRPα) expressing myeloid cells. Targeting of CD47 remains challenging because ubiquitous CD47 expression on healthy cells causes on-target off-tumor related toxicities and functions as an antigen sink. To locally restrict CD47 blockade to the NB tumor site, we successfully developed aGD2-SIRPα fusion mAbs for the murine and human setting. This data repository contains: - Flowcytometry data characterizing the binding of aGD2-SIRPa fusion mAbs to human and murine (NB) tumor cell lines and their CD47 blocking potential - Data from flowcytometric human and murine phagoctyosis assays - ELISA data to determine cytokine expression - NK-cell mediated killing of NB tumor cells by aGD2-SIRPa data