In this research proposal, we aim to investigate the feasibility of NK cell immunotherapy by evaluating the expression of activating and inhibitory NK cell receptor ligands on primary tumor cells. Furthermore, we aim to evaluate the cytotoxic…
ID
Source
Brief title
Condition
- Plasma cell neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
If the BM sample is infiltrated by NBL cells, the expression of activating NK
cell receptor ligands on the tumor itself; such as MIC (MICA/B) and ULBP
(ULBP1-4) proteins and CD112/ -CD155 as well as the expression of HLA class I
(inhibitory ligand), CD54/ -CD58 (adhesion) will be evaluated by FACS analysis
using multiple markers.
NK cell sensitivity will be determined by labelling primary NBL cells with 51-
Chromium or by chemo luminescent methods and adding resting and cytokine
activated NK cells. Furthermore, if NK cell cytotoxicity occurs, activating NK
cell receptors will be blocked by monoclonal antibodies (NKG2D, DNAM-1),
thereby allowing analysis of the activating signals involved.
Peripheral blood samples of newly diagnosed, untreated NBL patients will allow
analysis of NK cell phenotype and function in these patients at time of
diagnosis.
Secondary outcome
N/A
Background summary
The defining characteristics of high risk (HR) NBL include an age of more than
one year, with regional or metastatic disease, unfavourable Shimada histology
or Myc-N amplification (NMA). Patients with HR NBL have a 5-year survival rate
of only 30-40%, even if there is a favourable response to initial therapy.
For the majority of patients with relapsed refractory solid tumors, there are
currently no further treatment options other than phase I/ II studies or
palliation. Therefore, we aim to explore the feasibility of adoptive
immunotherapy (AIT) as an additional treatment modality for this tumor, with a
focus on natural killer (NK) cells.
Study objective
In this research proposal, we aim to investigate the feasibility of NK cell
immunotherapy by evaluating the expression of activating and inhibitory NK cell
receptor ligands on primary tumor cells. Furthermore, we aim to evaluate the
cytotoxic potential of unstimulated and cytokine stimulated NK cells towards
primary NBL tumor cells.
Cytotoxic activity of NK cells towards NBL cells in vitro and additional
stimulation methods (cytokines, irradiation, tumor manipulation) would further
substantiate a role for NK cell AIT of high risk NBL. This will encourage the
development of novel AIT strategies as an additional treatment for high risk or
relapsed NBL next to conventional or other novel therapies.
Study design
Prospective analysis, in newly diagnosed high risk neuroblastoma patients, of
bone marrow (BM) samples that are infiltrated with NBL cells and NK cells
obtained from blood, in order to perform immunological analysis.
Study burden and risks
No additional burden, risks, the patients will undergo a bone marrow aspirate
and bloods will be taken as a routine procedure in an newly diagnosed patient
(once).
In this study additional material will be taken during the same procedure:
bonemarrow 3-5 ml and blood 10-20 ml
meibergdreef 9
1105 AZ Amsterdam
NL
meibergdreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
High risk neuroblastoma, between 1 and 21 years at diagnosis.
Neuroblastoma histological proven diagnosis
informed consent
Initial staging of the tumor
No pregnancy
Exclusion criteria
Any prior or concomitant non-protocol anticancer treatment
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL28524.018.09 |