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 (ExpiNKT1)

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.

Study Overview

• Status: Unknown
• Conditions: Allogeneic Hematopoietic Stem Cell (HSC) Transplantation

• Study Type: Observational
• Enrollment (Anticipated): 134

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

healthy donors of HSCT

Description

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)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Kinetic of iNKT cells (flask culture)	from day 0 to day 14
time of culture to reach the maximal expansion factor	day 14
Percentage of cells alive	day 14
Percentages of CD4- iNKT cells capable of producing IFN-γ after expansion	day 14

Secondary Outcome Measures

Outcome Measure	Time Frame
Kinetic of iNKT cells(culture in bioreactor system)	From day 0 to day 14
Expression of cytokine receptors CD4- iNKT data	day 14
Expression of cytokine receptors CD4+ iNKT data	day 14
transcriptional pattern CD4- iNKT data	day 14
Transcriptional pattern CD4+ iNKT	day 14
Percentage of recovery of CD4- iNKT cells after immunomagnetic selection	day 14
Proportion of Th1 producing T cells stimulated by allogeneic dendritic cells	day 6 in a mixed lymphocyte reaction
Proportion of Th17 producing T cells stimulated by allogeneic dendritic cells	day 6 in a mixed lymphocyte reaction
Proportion of mice protected from GVHD mortality in a xeno-GVHD mouse model	survival proportions between day 28 and day 60 post-transplantation
Ratio of iNKT/T cells to control xeno-GVHD mortality	survival proportions between day 28 and day 60 post-transplantation
Proportion of mice protected from leukemia development	survival proportions between day 28 and day 60 post-transplantation

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 1, 2018
• Primary Completion (ANTICIPATED): October 1, 2019
• Study Completion (ANTICIPATED): April 1, 2021

Study Registration Dates

• First Submitted: July 21, 2018
• First Submitted That Met QC Criteria: July 27, 2018
• First Posted (ACTUAL): July 30, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 30, 2018
• Last Update Submitted That Met QC Criteria: July 27, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: immunotherapy; Hematology; Cell therapy; immuno-modulation
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: PRTK2017/ExpiNKT-RUBIO/VS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No