Advancing Precision Immunotherapy for Paediatric Leukaemia with Alice Giustacchini and her Group

Meet Alice Giustacchini, Research Group Leader in Population and Medical Genomics. Her project, titled “Tailoring Precision Immunotherapy to Paediatric Acute Myeloid Leukaemia,” aims to study the cellular and molecular dynamics of CAR-T cell therapy in blood cancers. Alice has recently received an AIRC Start-Up Grant worth 200,000 euros per year for five years, with a review after the third year. The five-year AIRC Start-Up Grants are awarded to researchers establishing their research lab in Italy after gaining significant experience abroad.

Alice, can you explain your project’s main objective?

Paediatric Acute Myeloid Leukaemia (AML) is a rare but aggressive disease with a poor prognosis, and outcomes have not significantly improved in the last three decades; it is also distinct from its more prevalent and extensively studied adult counterpart, requiring the development of specific treatment strategies. Unlike some other childhood leukaemias, it is highly heterogenous from patient to patient, making treatment particularly difficult. Standard chemotherapy often fails, and relapse is common, with poor survival rates. A key reason for this is the presence of leukaemia stem cells (LSCs), a small population of cells that resist chemotherapy and are responsible for the disease returning.

This project aims to develop a new, personalised cell therapy for paediatric AML, focusing on targeting these leukaemia stem cells to prevent relapse. Using cutting-edge multi-omic technologies, we will study how AML cells evolve and escape the immune system, identifying weaknesses that can be targeted with immunotherapy. We will also use 3D bone marrow organoid models to study how leukaemia cells interact with the immune system and find ways to overcome their resistance to treatment.

To translate this research into therapies, we will build on insights from ongoing cell-based immunotherapy trials, particularly those using Chimeric Antigen Receptor (CAR) therapies. CAR-based therapies work by reprogramming immune cells to recognize and attack leukemia cells based on specific antigens present on their surface. However, since AML is highly heterogenous and no single target works for all patients, we aim to design a framework for multi-targeted CAR therapies, ensuring they remain effective against different forms of the disease. Importantly, this strategy is not limited to AML—our approach could be adapted to other blood cancers and even solid tumors, making it a powerful tool for advancing personalized cancer treatment.

Who are your collaborators?

This project involves collaboration with some of the leading institutions in paediatric leukaemia and immunotherapy, including Great Ormond Street Hospital (GOSH), University College London in the UK and Ospedale Pediatrico Bambino Gesù in Italy.

Within Human Technopole, we collaborate with several groups within the Genomics and the Computational Biology research centres and national facilities, including the National Facility for Genomics, the National Facility for Genome Engineering and Disease Modelling, the National Facility for Light Imaging and the Flow Cytometry sunit.

Furthermore, the grant will fund a PhD student and a postdoctoral researcher. Their work will focus on genomic and immune profiling of patient samples, as well as developing functional and computational models to study disease progression and refine therapy strategies.

What are the main challenges and how will you overcome them?

One of the biggest challenges in treating AML is its high heterogeneity—there is no single target that works for all leukemic cells and in all patients. To address this, we will focus on a multi-targeting strategy, ensuring that CAR therapies can adapt to different types of AML and reduce the risk of resistance.

Another major challenge is that leukaemia cells actively suppress the immune system, making it difficult for immune therapies to work effectively. By using our 3D bone marrow organoid models, we will study how AML cells interact with immune cells and identify ways to restore immune function and enhance CAR T-cell effectiveness.

Finally, by studying patient samples from existing multitargeting CAR T-cell trials, we will learn from real-world treatments—understanding why some therapies succeed while others fail—to refine our approach and maximise treatment success.

What impact do you hope to achieve with this project?

This project is not just about developing a new therapy for paediatric AML—it is about creating a framework for the design of personalised cell therapies that can be applied to other diseases. By designing a strategy that targets multiple aspects of AML, we aim to move beyond standard, one-size-fits-all treatments and instead develop more precise therapies tailored to group of- and even individual patients.

This project fits within a broader trend towards precision medicine, where treatments are tailored to the unique biology of each patient’s disease.

Why are you excited about this AIRC Start-up grant?

I am excited that this AIRC Start-up grant will allow us to bridge the gap between leukaemia stem cell biology and precision immunotherapy. Also, I am grateful that, as part of this funding, our lab gets to join the outstanding AIRC community, dedicated to advancing cancer research in Italy.

Paediatric AML remains one of the most difficult childhood cancers to treat, with high relapse rates and limited options for children who do not respond to chemotherapy. Despite advances in treating other blood cancers, survival rates for AML remain among the lowest, highlighting the urgent need for novel approaches.

By looking at one cell at a time and one patient at a time, we aim to develop personalised treatments that are precisely tailored to each patient unique disease, with the potential of making a real difference for them and their family.