Molecular-genetic Characterization in Patients Undergoing CAR-T Cell Infusion

Condition(s) studied

Study summary

In recent years, the application of increasingly advanced methods of ex-vivo cell culture and cell engineering has made it possible to develop new cellular therapeutic platforms including the "CAR (Chimeric Antigen Receptor) - T cell therapy". CAR-T cell therapy is a therapy that uses T lymphocytes engineered to express a chimeric receptor directed against a specific antigen, theoretically applicable to the treatment of all neoplasms but currently more widely used in the treatment of haematological malignancies. One of the most innovative aspects introduced with CAR-T cell therapy is that of living-drug, cells that act as a drug as well as a means to build specific immunity against the neoplasm. The advantages of this therapy are therefore represented by the possibility of refueling the patient's immunity, deficient in the control of the neoplastic disease, with lymphocytes capable of expressing an antineoplastic activity with mechanisms not subject to restriction of HLA-mediated antigen recognition.

However, the use of CAR-T therapies is not free from potentially serious and sometimes lethal adverse events; in the toxicity profile the following are recognizable as peculiar:

* cytokine release syndrome (CRS)
* B-cell aplasia (hypogammaglobulinemia)
* neurological adverse reactions
* haematological toxicity
* infections. Therefore, considering that on the one hand adverse events are not negligible and on the other hand that a percentage \> 50% of patients lose the response obtained, it is necessary to improve the therapeutic profile of CAR-T cell therapy by increasing its efficacy and reducing its toxicity . Both of these strategies are linked to the understanding of the resistance mechanisms of neoplastic cells, as well as to the biology of CAR-T cells and of all the cellular (microenvironment) and non-cellular systems with which they interact.

Eligibility

Primary outcome measure(s)

• Genomic studies — 3 years
  Genomic studies in peripheral blood samples taken from patients affected by hematological malignancies undergoing CAR-T cell therapy, in order to identify correlations between neoplastic cell signatures and response to therapy (evaluated according to laboratory and instrumental standards).
• Study of CAR+ and CAR- lymphoid populations and of myeloid populations — 3 years
  Study of CAR+ and CAR- lymphoid populations and of myeloid populations with single-cell RNA sequencing platforms in peripheral blood samples in order to understand the cellular dynamics related to clinical outcomes such as response to therapy (evaluated according to laboratory and instrumental standards) and adverse events (CRS, ICANS, sHLH, coagulopathy, cytopenias, and autoimmune dyscrasias).

Trial sites (1)

More IRCCS Azienda Ospedaliero-Universitaria di Bologna trials in Italy

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