Cancer Research Institute (US) grant (200kE) for Martijn den Brok and Gosse Adema

Brok den, Martijn

Martijn den Brok (left) and Gosse Adema (right) from the department of Tumor Immunology in collaboration with Yona Keisari from the Sackler Faculty of Medicine, Tel-Aviv University, Israel have received a grant (200 KE) from the Cancer Research Institute (US).   

Adema, Gosse









The grant aims (see abstract of the grant):

Exploiting in situ tumor destruction techniques for the in vivo modulation of anti-tumor immunity

In situ tumor destruction (ablation) techniques- are successfully applied for the treatment of cancer. Although diverse in their ways to induce cell death, ablative techniques share one key feature: thein situavailability of ablated material that potentially contains tumor antigens for the induction of anti-tumor immunity. We showed independently in murine models for cryo-ablation, radiofrequency-ablation and the new technique pulsed electric current-ablation (PECTA), and Diffusing alpha-emiters Radiation Therapy (DaRT) that each method reduced metastatic load and increased protection to subsequent tumor rechallenges, suggesting the induction of tumor-specific immune responses. For cryoablation we demonstrated the involvement of lymph node dendritic cells, that actively scavenged antigens from the tumor debris for presentation to effector immune cells. To boost the weak immune response following ablation we combined ablation with peritumoral injection of adjuvants like the TLR9-ligand CpG-ODN, which matured DCs and led to synergistic immune responses and protection. It is currently not fully understood how immune responses following ablation are regulated. More importantly, data is lacking about which ablation technique provides the most effective antigen release and the most immune stimulating micro-environment.

In this collaboration we propose a direct comparison of the aforementioned ablation techniques in a context of anti-tumor immunity. We will monitor tissue destruction and release of antigens, mobilization/activation of immune cells, as well as immunological outcome. Concurrently, we will investigate the combinatorial effects of local immune modulation.

The project will provide vital insights in the ablation-related determinants that lead to effective immune response induction, and that combine synergistically with immune modulators.

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