Expansion of Invariant NKT Cells for a Cell Immunotherapeutic Approach Allowing the Control of Graft Versus Host-disease and Preserving the Graft Versus Leukemia Effect After Allogeneic Hematopoietic Stem Cell Transplantation

NCT ID: NCT03605953

Last Updated: 2018-07-30

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 134 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-10-01
• Study Completion Date: 2021-04-01

Brief Summary

Allogeneic hematopoietic stem cell (HSC) transplantation remains the most efficient cellular immunotherapeutic approach for the treatment of myeloid hematological malignancies. However, its use is hampered by the risk of developing acute graft-versus-host disease (aGVHD). Invariant NKT cells (iNKT) represent a good candidate of immuno-regulatory cells that could control GVHD while preserving the anti-leukemic effect (GVL) of HSCT. Our team have shown that higher numbers and expansion capacity of CD4- iNKT cells contained in the HSC graft were associated with reduced risk of aGVHD but preserved GVL effect and that some healthy donors have low numbers and expansion capacity CD4- iNKT cells 1.

The objective of this project is to develop a strategy allowing to expand human CD4- iNKT cells from healthy donors of HSC grafts that would be transposable to GMP-validated cell production. Our team proposes to first determine the best strategy to expand the CD4- iNKT cell subset from G-SCF mobilized peripheral blood stem cells (PBSC) obtained from healthy donors, at little scale using cultures GMP validated conditions, by comparing the convention expansion protocol using IL-2 alone to IL-7, IL-15, IL-4 or combination of those cytokines involved in the expansion of T cells and by culturing the cells in a bioreactor. Our team will then explore the characteristics of cells after expansion in terms of phenotype, transcription signature and functions in vitro (in mixed lymphocyte reaction) and in vivo in a well-established xenogeneic model of GVHD.

Conditions

Allogeneic Hematopoietic Stem Cell (HSC) Transplantation

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

Hematopoietic stem cells :

• from major donors after mobilization by G-CSF, informed of the research and not having opposed it
• Collected after verification by the cell therapy centre of the presence of a sufficient quantity of CSH for transplantation

Exclusion Criteria

Hematopoietic stem cells (HSCs) from donors seropositive for HIV, HCV, HTLV1 and HBV (except post-vaccination profile)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Central Hospital, Nancy, France

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Marie-Thérèse RUBIO, PU-PH

Role: CONTACT

m.rubio@chru-nancy.fr

0383153282 ext. +33

Other Identifiers

PRTK2017/ExpiNKT-RUBIO/VS

Identifier Type: -

Identifier Source: org_study_id