Isolation, immortalization and characterization of human B lymphocytes for the development of diagnostic and therapeutic antibodies against cancer.

In the defense against cancer the immune system plays an important role. In
healthy individuals, the innate and the adaptive immune systems collaborate to
recognize and eliminate developing tumor cells, thereby preventing the
outgrowth of tumor cells (reviewed recently by Schreiber ea, Science
2011;331:1565-1570). A well known clinical example of immune mediated tumor
regression is the development of vitiligo in melanoma patients, through the
recognition and killing of healthy pigment bearing cells in addition to the
recognition and killing of melanoma cells. Another clinical example of
anti-tumor immune responses are patients with hematologic tumors who receive an
allogenic stemcell transplantation, to induce a sustained graft versus leukemia
(or lymphoma) response. Similar to melanoma patients, this graft versus
leukemia response is often accompanied by an immune response against healthy
cells, resulting in graft versus host disease, where the donor immune system
also mounts an immune response against otherwise healthy organs such as
intestine, skin and liver.

Until recently, the field of anti-tumor immunology has focussed on the role of
T lymphocytes. Recently, however, the group of prof. H. Spits and dr. T.
Beaumont developed an in vitro methodology to grow human, monoclonal, B cell
receptor positive and immunoglobulin secreting B cells (AIMSelect). With this
method it has now become possible to study the role of B lymphocytes in
anti-tumor immune responses.

The objective of the current study is to identify, develop and produce tumor
specific antibodies with the goal to:
1) further characterize the role of B cells in anti-tumor immunity; and to
2) develop human monoclonal tumor specific antibodies for diagnostic and
therapeutic purposes.

Our research focusses on three malignancies : hematologic malignancies,
melanoma and gastro-intestinal tumors.

We will recruit patients who developed an anti-tumor response against one of
the above mentioned malignancies. Of these patients, B lymphocytes will be
isolated from one single draw of peripheral blood that is collected through
venapuncture. These cells will be immortalized in vitro, after which monoclonal
B cell lines and antibodies specifically directed against the tumor cells will
be selected, isolated and grown. After characterization of the specific antigen
on the tumor cells, the antibody functionality will be tested (in vitro and in
mouse models). In a seperate study (for which we do not ask for approval here)
we will study the presence of these antibodies in serum of larger series of
patients and test whether these antibodies can play a role in diagnosis of
anti-tumor responses. Details of the AIMSelect method are described in
Kwakkenbos ea, Nature Medicine 2010;16:123-128.

Burden for participants
Single blood draw through venapuncture (55-65 ml; 6-8 tubes).

Risk associated with participation:
Neglectable (venapuncture-induced hematoma)

Benefit:
There is no direct benefit for the participants. There is a group benefit
though; if we do find tumor-specific monoclonal antibodies that can be used in
clinical practice, as a diagnostic tool (to assess tumor response for example
after allogeneic stem cell transplantation) or as a therapeutic tool, this will
be of benefit to cancer-patients in general. In any case these studies will
improve our understanding of cancer-immunology, which is also beneficial to
cancer patients as a group.