3 Types of Cancer Vaccines Explained

[Guest guest]

Dear Readers: This is reprinted (with permission)

from an non-Hodgkin's lymphoma e-mail list. The

author is Lurdes Queimado, an MD and medical

researcher whom I have met with twice at the Lymphoma

Research Foundation of America's Advocacy Day in

Washington, DC.

She is very knowledgeable and has a personal interest

in lymphoma, since her husband has NHL.

From: queimado.lurdes@...

Subject: main types of Idiotype vaccines

I wrote this for another group but may be some on this

group are also interested on it. Lurdes Queimado

Dear all, Answering a request here is a summary of the

main types of idiotype vaccines being currently used

in NHL.

The so-called Idiotype vaccines are vaccines that try

to " educate " patient's immune system to recognize an

idiotype protein that exists on the surface of

lymphoma cells and is patient specific. Essentially

every patient with a B cell lymphoma has an idiotype

protein in his or her lymphoma cells. However, this

protein is different in each patient. Keep in mind

that there are other types of vaccine for NHL that do

not specifically to induce an immune response against

the idiotype protein.

An example is the use of autologous tumor-derived

HEAT-shock protein peptides (trial in Huston). You

also can find additional information, including

considerations about adjuvants, the techniques used,

and the papers mentioned below at

http://www.datafork.com/vaccines.htm.

Specific points about the phase III vaccine trials

have been (and are still) questioned. Our letters to

Dr. Kwak and other leader scientists in the field can

be read at http://www.datafork.com/lymphoma.htm

IDIOTYPE VACCINES FOR NHL: There are 3 main types of

vaccines in trials: DNA vaccines, " protein " vaccines

and dendritic cell vaccines. All cases require a

supply of tumor cells, collected usually by lymph node

biopsy. 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, 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 or leg. 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.

The " protein " vaccines (I am 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 has 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. The bacteria

(or virus) will then produce a lot of idiotype protein

that the scientists collect and inject in the patient.

(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. 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.).

The 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 few places and the number of patients

accepted 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 complete

remission (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.

Lurdes

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