Christian Ottensmeier - Overview
Translational research –DNA vaccination
While the treatment of lymphomas and of solid tumours has undergone significant
changes over the last decades, many patients with these cancers still
have incurable disease. More recently the classical treatment modalities
of are being complemented by new approaches, which focus on activating
the immune system aginst the cancer present in the patient.
In close collaboration with the laboratory of Prof.
Freda Stevenson, this programme links basic laboratory research to its
application in a clinical setting, carrying the research "from the
bench to the bedside". The objectives are to carry forward the development
and application of DNA vaccines in B cell malignancies in several clinical
phase I/II triald and to define the applicability of DNA vaccines to the
treatment of solid tumours.
The focus is
- Integration of the laboratory and clinical aspects of the DNA vaccine
studies in patients with follicular lymphoma, chronic lymphocytic leukemia
and multiple myeloma currently underway
- Measurement of in vitro/in vivo responses to the DNA vaccine in patients
- The development of a DNA fusion vaccine against carcinoembryonic antigen
(CEA), which is abundantly expressed on a variety of human cancers, including
those of the colon, rectum and stomach
- Modification of the current DNA fusion vaccine to enhance specific
immune functions
- Preparation of a DNA vaccine study with a CEA-fusion construct in patients
with metastatic colorectal cancer
Immunogenetics of B cell malignancies
The analysis of the immunoglobulin (Ig) genes in B-cell tumours has shed
new light on the events which shape the malignant cell. Ig gene rearrangement,
somatic mutation and class switching leave their traces in the Ig-genotype
of a B-cell and Ig analysis can provide important information about the
clonal history of the malignant B-cell. Evidence for ongoing somatic mutation
can be identified by detecting micro-heterogeneity in the clonally-related
sequences from the tumour. While the clonal fingerprint of the tumour
is shared between all cells, some cells have acquired additional mutations,
not shared by other cells. This type of pattern is found in Follicular
Lymphoma (FL) and Diffuse Large B-cell Lymphomas (DLBCL). Interestingly
the tumour cells of DLBCL and FL are also able to produce transcripts
for more than one Ig isotype. This provides additional evidence that the
malignant tumour cells are much less frozen in their development, than
previously thought.
We have recently observed the introduction of novel
glycosylation sites into the V genes of FL. These sites are observed in
the vast majority of FL, but rarely in normal B cells. This suggests that
glycosylation may play a role in the development and clinical behaviour
of FL.
Ongoing work focusses on diffuse large cell lymphomas
of special sites (like the CNS) and investigates the ability of FL and
DLBCL to undergo class switching events.
