Lymphoma

Lymphoma is a type of cancer
involving cells of the immune system,
called lymphocytes. Just as cancer
represents many different diseases,
lymphoma represents many different
cancers of lymphocytes -- about 35
different subtypes, in fact.

Lymphomas fall into one of two major
categories: Hodgkin's lymphoma (HL,
previously called Hodgkin's disease)
and all other lymphomas (non-
Hodgkin's lymphomas or NHLs).

About 8,500 patients in the U.S. each
year are diagnosed with Hodgkin
lymphoma, a cancer that affects white
blood cells. Most of these patients are
treated successfully with a four-drug
chemotherapy cocktail or stem-cell
transplants.



FDA APPROVES NEW LYMPHOMA
DRUG, ADCETRIS
In August 2011,  offering hope to
lymphoma patients who have
exhausted their treatment options, the
Food and Drug Administration  
approved a new drug.

Brentuximab vedotin (SGN35), now
sold as Adcetris, was developed using
a monoclonal antibody that Eckhard
Podack, M.D. generated in 1992 that
targeted CD30, a molecule prominently
displayed on some lymphomas.

In 1999, the University of Miami
licensed the antibody to Seattle
Genetics, which paired it with a potent
cell-killing agent, monomethyl
auristatin (MMAE), creating a novel
biologic therapy that seeks out CD30
and delivers MMAE to cancer cells
while leaving healthy tissue alone.

In initial phase 1 and phase 2 trials  
many patients  who failed standard
therapies went into complete remission.

“This agent is the first new treatment in
years for CD30-positive lymphomas
that have failed standard therapy,
which is important for patients who did
not benefit from chemotherapy and
autologous transplant,’’ said Joseph
Rosenblatt, M.D., principal investigator
of trials testing SGN35. “SGN35 shows
great promise for patients with poor
prognoses.”

The compound has a novel
mechanism of action for a Hodgkin
lymphoma drug.  It combines an
antibody with a chemotherapy drug.
The antibody binds to the CD30-
positive Reed-Sternberg cells that are
characteristic of the disease, while the
drug -- monomethyl auristatin -- then
attacks the internal structure of the
cells.

Adcetris is an antibody conjugate. It is
a cell-killing drug attached to a type of
cancer-targeting antibody so that the
drug seeks the cancer and kills it. The
theory is that harmless cells aren't
affected, thus lowering the drug's
toxicity.



LYMPHOMA B-CELL STUDY AIMING
AT FURTHER INMPROVEMENTS
Mature B-Cell Lymphoma And
Leukemia Study III.
This is a phase II/III clinical trial using
risk-adapted therapy. Treatment
outcomes for children with B-cell NHL
are excellent. Further improvements in
outcome will likely be achieved through
more focused study of the biology of
the tumors and prospective studies of
the late effects of treatment. Toward
this end, this study features a
spectrum of prospective biologic and
late effect studies performed in
patients treated with a modified
regimen derived from the very
successful LMB-96 regimen.

B cells are an essential component of
the adaptive immune system.The
principal functions of B cells are to
make antibodies against antigens,
perform the role of antigen-presenting
cells (APCs) and eventually develop
into memory B cells after activation by
antigen interaction.

An antigen is a molecule recognized by
the immune system.  "Self" antigens
are usually tolerated by the immune
system; whereas "Non-self" antigens
are identified as intruders and
attacked by the immune system.

Autoimmune disorders arise from the
immune system reacting to its own
antigens.


BIOVAXID VACCINE TESTED FOR
NON-HODGKIN LYMPHOMA
A phase III clinical trial for treating
follicular lymphoma (a type of non-
Hodgkin lymphoma) with the cancer
vaccine BiovaxID showed remission
time to be increased by just over a
year.

Biovest is  a biotechnology company
focusing primarily on the development
of BiovaxID, a patient-specific anti-
cancer vaccine focusing on the
treatment of follicular non-Hodgkins
lymphoma, or follicular NHL.

Follicular NHL is a cancer of the
lymphatic system that results when the
body’s follicle center cells, which are a
type of white blood cell, become
abnormal and eventually spread
throughout the body growing and
dividing in an uncontrolled fashion.

BiovaxID is a customized anti-cancer
vaccine that is derived from a patient’s
own cancer cells and is designed to
utilize the power of the patient’s
immune system to recognize and
destroy cancerous lymphoma cells
while sparing normal cells.

This vaccine is produced by extracting
some of the patient’s tumor cells and
then replicating and purifying the
unique antigen that is present only on
the surface of the patient’s own tumor
cells.

The company is  currently conducting
a pivotal Phase 3 clinical trial for
BiovaxID in patients with the indolent,
or low-grade, form of B-cell follicular
NHL.

Patients are subsequently studied to
observe their immune responses both
to the non-specific immune stimulating
agents and for the specific immune
response to the vaccine.

Patients are followed for a minimum of
4 years post-randomization or until
relapse.


BAYER'S PLANT-BASED VACCINE IN
PHASE 1 TRIAL FOR LYMPHOMA
Bayer Innovation GmbH,   following the
Phase I study   in the United States, is
now testing the vaccine  in human
subjects. This is the first time that
proteins obtained from tobacco plants
using magnICON  technology undergo
clinical testing. The patient-specific
vaccines produced in the pilot plant
operated by the Bayer-subsidiary Icon
Genetics in Halle, Germany, are
intended for the treatment of non-
Hodgkin's lymphoma (NHL), a type of
cancer affecting lymphocytes. The
objective of the therapy is to activate
the patient's immune system, enabling
the malignant cells to be targeted and
destroyed by the body's own defense
system.

"This personalized vaccine is being
developed with the aim of keeping
patients who have responded well to
chemotherapy in complete remission,"
explains Dr. Detlef Wollweber, head of
Bayer Innovation GmbH. "In other
words, it should prevent a recurrence
of the tumor. The initiation of this
clinical trial also demonstrates that our
magnICON technology is suitable for
manufacturing proteins for potential
pharmaceutical applications."

The magnICON technology is a new
process for the rapid production of
high yields of recombinant proteins
such as biopharmaceuticals in tobacco
plants. The plant is not genetically
modified: The blueprint for the
required product is inserted
temporarily into the plant using a
species of Agrobacterium and
distributed throughout the plant cells.
The protein is subsequently be
extracted from the plant's leaves in a
very pure form. The process can also
be carried out in a large-scale closed
facility.

Scientists have been trying to trigger
an immune response to this type of
patient-specific idiotypic antibody
(surface immunoglobulins) since the
1990s in the hope of substantially
delaying the recurrence of the tumor.
In 2006 a team of researchers working
with Professor Maurizio Bendandi at
the University of Navarra (Spain),
succeeded in this objective in a
groundbreaking research study
involving patients who had previously
achieved complete remission with
chemotherapy. Bayer's new Phase I
study is carried out in close
cooperation with Bendandi.
The Phase I clinical study which has
just started is being performed at the
renowned University of Texas
Southwestern Medical Center in Dallas
(United States).