On the road to personalized immunotherapy: an unexpected journey

Chiara M. Cattaneo

Research output: ThesisDoctoral thesis 2 (Research NOT UU / Graduation UU)

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Abstract

Cancer immunotherapy has transformed the treatment for advanced cancers. However, durable responses to the treatments are rare events. To further improve the efficacy of current cancer immunotherapies, it is necessary to find ways to predict which patient is most likely to respond or not to the treatment, who is likely to eventually relapse, which resistance mechanisms will arise and how to overcome these mechanisms. 
To achieve those goals we generate two new model systems to study the interaction between tumor cells and immune cells, for the individual patient: the coculture and the HANSolo platforms. 
The coculture is a platform to train the immune cells of the patient to recognize and kill the tumor cells. First, starting from a biopsy, we generate tumor organoids, a three-dimensional model of the patient tumor that can be cultured in the laboratory. Next, the patient immune cells, isolated from a vial of blood, are trained (in coculture) with the tumor organoids, to become reactive against the patient tumor cells. We demonstrated the feasibility and physiological value of this approach. Furthermore, we explore possible applications of this model system in the development of new drugs.
A reactive immune population is powerful, but also dangerous; it is important to know the target of that reactivity, to avoid any side effects. HANSolo is a platform that combines the use of patient derived material and new sequencing technology to discover what are the molecules recognized on the surface of a tumor cells by the immune system. 

Original languageEnglish
Awarding Institution
  • University Medical Center (UMC) Utrecht
Supervisors/Advisors
  • Voest, EE, Primary supervisor
Award date15 Apr 2021
Publisher
Print ISBNs978-94-6419-181-3
DOIs
Publication statusPublished - 15 Apr 2021
Externally publishedYes

Keywords

  • Neoantigens
  • Immunotherapy
  • Personalized medicine
  • Precision medicine
  • Tumor organoids
  • CRC
  • NSCLC

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