2ⁿᵈ Edition of the Cancer R&D World Conference 2026

Abstract

In recent years, immunotherapy has emerged as a significant approach for treating cancer by harnessing the body’s immune system to target cancer cells. Among various strategies, antibody-based therapy, particularly monoclonal antibodies (mAbs), has shown efficacy against aggressive cancers. However, their effectiveness is hindered by poor pharmacokinetics and difficulty in crossing biological barriers. H-Ferritin nanoparticles (HFn) offer promise in addressing these limitations by enabling targeted drug delivery. HFn is biocompatible and capable of recognizing the transferrin receptor 1 (TfR1) overexpressed in solid tumors. Our research has demonstrated the effectiveness of HFn as a carrier to enhance mAbs’ crossing of the blood-brain barrier while retaining their antitumoral activity in 2D tumor models. More recently, our effort has shifted towards assessing the efficacy of HFn-mAb nanoconjugates in 3D cellular models.

We chose spheroids as 3D model because they mimic key features of human solid tumors, including spatial architecture, cellular organization, physiological responses, and nutrient gradients. Our initial experiments focused on optimizing the formation of cancer spheroids from glioblastoma and breast cancer cells, as well as assessing the internalization of HFn-mAbs using flow cytometry. We investigated the ability of HFn-mAb nanoconjugates to induce antibody-dependent cellular cytotoxicity (ADCC) using Operetta live imaging system to monitor apoptosis activation and mortality increase over time. ADCC stimulation was confirmed by studying the activation of natural killer cells, which release cytotoxic granules upon binding to the Fc portion of mAbs, leading to cancer cell death.

Preliminary in vivo experiments revealed preferential accumulation of the nanoconjugate at the tumor site. The data from our 3D models demonstrated the efficacy of HFn-mAbs in triggering anticancer effects and activating the immune system. Co-administering HFn-mAb with Doxorubicin or Cisplatin-loaded Ferritin is expected to synergize immune system activation with the chemotherapeutic activity of these drugs, The anticancer effect of such combination therapy will be assessed in vivo.