main types of vaccines in trials:
Idiotype "Protein" vaccines
Dendritic cell vaccines
Heat shock proteins vaccine
In all cases there is need for tumor cells, collected usually by lymph node
biopsy and the vaccine is made specifically for each patient.
The DNA vaccines are the simplest to explain but they are also the least
studied. To prepare these vaccines RNA is extracted from a tumor sample (node or even
FNA-Fine Needle Aspiration), the RNA corresponding to the idiotype protein is identified
and sequenced, and that sequence is integrated into another piece of DNA (vector). The
vector containing the sequence for the idiotype protein is injected in the patient's arm
The hope is that somehow the patient's immune system will start to recognize the
idiotype protein as strange. As far as I know, no results have been published concerning
trials in lymphoma patients with these vaccines. However, studies in animal models
strongly suggest that they will be effective. If they become effective this will be a
major advance as they are "very cheap" by comparison with the remaining types.
Idiotype "protein" vaccines
giving them this name, but they are worldwide referred only as the idiotype vaccines,
because they were the first to be developed and for a many years they were the only
available). The initial procedure is exactly as described before. However, instead of
injecting the vector with DNA into the patient's arm or leg, the vector is put inside of a
bacteria (transformation) or a virus. There are bacteria (or virus) will them
produce a lot of Idiotype protein that the scientists will collect and inject in the
Note: there are many ways of producing protein and I am not trying to
explain all. Also, the original process used in the first trial published by Dr. Levy was
much more complicated. These idiotype vaccine have already produced dramatic
long-term clinical remissions for patients with NHL (Hsu FJ. Caspar CB. Czerwinski D. Kwak
LW. Liles TM. Syrengelas A. Taidi-Laskowski B. Levy R.Tumor-specific idiotype vaccines in
the treatment of patients with B-cell lymphoma-long-term results of a clinical trial.
Blood. 89 (9):3129-35, 1997).
Furthermore, one study has shown that the idiotype
vaccination can induce even molecular remissions (a hope for a cure) (Bendandi M. Gocke
CD. Kobrin CB. Benko FA. Sternas LA. Pennington R. Watson TM. Reynolds CW. Gause BL.
Duffey PL. Jaffe ES. Creekmore SP. Longo DL. Kwak LW. Complete molecular remissions
induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating
factor against lymphoma.
Nature Medicine. 5 (10):1171-7, 1999 Oct.).
dendritic cell vaccine is the most complex and expensive process. It is also
probably the most promising. However, because of the costs and because it requires a more
advanced technology is only being studied at very specific places and the number of
in these trials are even smaller than in other vaccine trials.
The first part of the process is essentially the same as described for the
"protein" vaccines however after the idiotype protein is collected from bacteria
this protein is used in vitro to stimulate the patient's dendritic cells. Dendrite cells
circulate in our blood and can be collected by apheresis.
Dendritic cells alert the immune
system of any bacteria or viruses that are in a person's body. In the dendritic vaccine
patient's dendritic cells are collected, grown in a solution that contained large amounts
of patient's idiotype protein (made in bacteria, for example). Therefore, these cells are
"educated" in vitro to recognize the patient's idiotype protein as foreign and
reinfused into the patient.
The dendritic vaccine has shown to be effective even if the
patients do not obtain CR (Hsu FJ. Benike C. Fagnoni F. Liles TM. Czerwinski D. Taidi B.
Engleman EG. Levy R. Vaccination of patients with B-cell lymphoma using autologous
antigen-pulsed dendritic cells. Nature Medicine. 2(1):52-8, 1996 Jan.).
Important: Theoretically, these vaccines may help in any patient with a lymphoma derived
from a B-cell. Although most of the studies
published and clinical trials concer follicular NHL, similar trials are also including
intermediate grade, mantle cell lymphoma and others.
Heat Shock Proteins
Vaccine "The versatility of
heat shock proteins in the treatment of cancer derives from their normal
physiological role in cells. HSPs play a role in protein trafficking,
whereby they keep other proteins in their correct shape and location. When
these molecular chaperones are purified from cells, they bring along with
them small fragments, or peptides, derived from other proteins expressed
in that cell, providing a molecular "fingerprint" of the cell's
content. Vaccination with the HSP-peptide complexes purified from cancer
cells has the potential to specifically stimulate the immune system to
attack cells bearing those peptides, i.e., the cancer cells themselves."
|Below is a technical subject explained
in plain language by Lurdes. Different methods have been developed to
create a vaccine that can "teach" the immune system about a
specific protein target on the patients tumor. The idiotype is a
good target protein because it's not expressed anywhere else but on the
patient's tumor cells. The job of isolating this protein and fusing it with
another molecule called KLH is an exceptional technical feat. The
following description by Lurdes explains that the idiotype itself is
complex and has multiple targets within it. -Karl
Polyclonal can be very confusing because it may signify different
An immune response against most proteins is usually polyclonal. David
was talking about a protein as a string of beads. Imagine that a specific
Id from patient A has 5 blue beads followed by 5 red beads followed by 5
green beads. If each stretch of 5 beads is immunogenic an immune response
of 3 different antibodies (one against green, another against red, another
against blue) might occur. Because there is more than one antibody it is
Imagine now that patient A has more than one type of Id (her
tumor has different clones). In this case even if a single antibody
is made for each different Id, the response is called polyclonal.
Therefore, when someone tells you that their vaccine has a polyclonal
effect you need to ask "is that against different Ids or against
different parts of the same Id?"
This is extremely important if a patient has more than a single Id. The
original vaccine was derived from a hybridoma, it was only against a
single Id, but it was against several different parts of that Id. That's
why is was called polyclonal.
In my mind the most important thing is that a vaccine is able
to produce an immune response against the different parts of a given
protein. For example, let's take the specific Id I described before (5
beads blue, 5 red, 5 green). When a patient has different Ids, they raise
by mutations in previous Ids. Let's say one blue bead changed to a black
bead. If that was the case the antibodies made against the blue
beads might not recognize this mutant, but the antibodies made against red
and green will still recognize
the mutant protein.
Another comment: The reason why the "old vaccine" is not being followed is
because it is extremely time consuming, expensive and has a high rate of
failures. Furthermore, it might be worse than some of the "new
vaccines". Both the Genitope and Favrille are in my opinion highly
promising. However, as you
said we do not have data. We are the "mice". One can choose to
wait until data is available or until he/she progresses, but that can be
too late. Alternatively, one can take the risk of taking a vaccine that
does not seem to have major risks but might do nothing. Each of us need to
weight the pros
- Lurdes Q