Testing of a new antibody therapy using blood from children with B-cell Non-Hodgkin lymphoma.

Rituximab, an anti-CD20 IgG monoclonal, is successfully used for treating
Non-Hodgkin B-cell lymphomas in adults. From 2010, reports of rituximab therapy
in children appear and in 2013 the Netherlands and the WKZ (Utrecht) joined in
a protocol to treat children or adolescents with B-cell lymphomas. Long-term
adverse effects of rituximab are, however, noted: permanent depletion of B
cells and inability of naïve B cells to switch to memory B cells, resulting in
life-long immunoglobulin depletion. The long persistence of IgG in the body and
the immature nature of the B-cell compartment in children is probably
accountable. Next to IgG, the IgA isotype is more effective as it can mediate
stronger and faster antibody dependent cell-mediated cytotoxicity (ADCC) in in
vitro/vivo experiments and it has a much shorter half-life, anticipated to
cause fewer side effects. In short, IgA would facilitate an effective blow to
the lymphoma but is cleared fast enough to allow a good recovery of the B-cell
repertoire.

Within the immunotherapy group, a new panel of anti-CD20 monoclonals have been
generated that are currently produced as chimeric IgG and IgA formats. We
intend to demonstrate the efficacy and the anticipated superiority of IgA
versus IgG and rituximab in their B cell depletion efficacy using in vitro
experiments with patient material.
Ultimately, by using anti-CD20 IgA, we aim to develop a better B-cell depletion
therapy for children with Non-Hodgkin B-cell lymphoma that has less or no long
term adverse effects.

1. Rest material from a lymphoma biopsy from a pediatric patient suspected for
Non-Hodgkin lymphoma will be preserved in the laboratory.

2. As soon as Non-Hodgkin lymphoma is diagnosed, the patient will be asked to
participate in our study and to donate a blood sample (<=30 ml).

3. The blood sample and the biopsy material from the same patient will
immediatly be used for experiments in the laboratory. Depending on the results,
we will adjust the setup of future experiments or the experiment will be
repeated as soon as new material becomes available.

4. All patient material will be destroyed within 24 hours after blood sample
aquisition.

We consider the burden for participation to be very low for the patient. There
is no benefit for the patient when participating in our study.
Our study depends on aquiring material from pediatric patients diagnosed with
CD20+ B-cell lymphoma and is therfore strongly related to this group.