DTA

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Tesi etd-10232022-155000

Type of thesis
Corso Ordinario Ciclo Unico 6 Anni
Author
ZUCCHINETTI, CRISTINA
URN
etd-10232022-155000
Title
CD4 CAR-T cells play a key role both in exacerbating cytokine release syndrome and maintaining long-term responses
Structure
Cl. Sc. Sperimentali - Medicina
Course
SCIENZE MEDICHE - SCIENZE MEDICHE
Committee
relatore Prof. PASSINO, CLAUDIO
Relatore Dott.ssa Casucci, Monica
Membro Prof. COCEANI, FLAVIO
Membro Prof. EMDIN, MICHELE
Membro Prof. LIONETTI, VINCENZO
Membro Prof.ssa CASIERI, VALENTINA
Membro Dott. AIMO, ALBERTO
Keywords
  • animal model
  • CD4 CAR-T cells
  • cytokine release syndrome
  • toxicity
Exam session start date
20/12/2022;
Availability
parziale
Abstract
In this last decade, cellular immunotherapy has gained a lot of interest in the scientific community. In fact, T cells redirected with CD19-specific chimeric antigen receptors (CAR) have revolutionized B-cell malignancies treatment. However, there are still many challenges to face: failures are still common and large-scale use is limited by the occurrence of severe toxicities. <br>Toxicities related to CAR-T cells include cytokine release syndrome (CRS) and neurotoxicity. The exact mechanisms involved are still unclear and different research fields are trying to shed light on them. <br>Different studies suggest that the composition of CAR-T cells product in terms of CD4-CD8 proportion has an impact on efficacy and toxicity.<br>In this project, we investigated how CD4 and CD8 populations cooperate during CAR-T cell responses and what is their specific role in CRS development. CD4 CAR-T cells showed superior proliferation and activation potential, triggering a stronger stimulation of myeloid cells, which plays a major role in the development of adverse events.<br>This observation found validation with in vivo mouse model: CD4 CAR-T cells are key contributors to CRS development, but also in guiding expansion kinetics and maintaining long-term responses.
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