Humoral Epitope-Spreading Following Immunization with a HER-2/neu Peptide Based Vaccine in Cancer Patients

"HER-2/neu is a tumor antigen in patients with breast and ovarian cancer. Multiple varieties of vaccine strategies are being developed to immunize patients against HER-2/neu. Studies in animal models have demonstrated both T cell and antibody immunity are needed to mediate an antitumor response. Thirty-five patients, immunized with HER-2/neu peptide based vaccines, were evaluated for the generation of HER-2/neu-specific antibody immunity. Sixty percent of patients developed HER-2/neu IgG specific antibody responses to at least one peptide included in their vaccine. Twenty-nine percent of patients developed IgG immunity to the native HER-2/neu protein after peptide immunization. Humoral intramolecular epitope-spreading within the HER-2/neu protein occurred in 49% of immunized patients. Intermolecular epitope-spreading to p53 was evident in 20% of vaccinated patients. Of those patients who developed new immunity to p53, 71% had demonstrated antibody epitope-spreading within HER-2/neu."

Sounds promising, but although obviously some bits need a bit of translating. What exactly is epitope-spreading?

Christine; I'll ask the doctors at UW when I go for my 3rd vaccine later this month...it'll be timely as at this visit they'll be drawing blood samples to measure my antibody response to the vaccine. I'll be very interested to get an explanation in laywoman's terms!
Thanks for a great article, sorry it took me so long to see it.

Love, Lolly

Hello Ladies,
I found this explanation on the web:

What is an Epitope?
Antibodies are raised by the immune system against regions on the surface of a protein known as Epitopes. An Epitope, or antigenic determinant, is defined as a region of 6-12 amino acid or carbohydrate residues to which an antibody can bind.
There are two types of Epitopes:
continuous
discontinuous
A continuous Epitope is composed of a contiguous stretch of residues in a protein. A discontinuous Epitope consists of a group of residues that are not contiguous in the sequence, but are brought together by the folding of the polypeptide chain, or by the juxtaposition of two separate peptide chains.

Soooo.... what does this all mean??
It seems that there are more than 1 antigen signatures that make-up HER/neu, and this particular vaccine has been able to activate epitopes across these antigens without having to be muti-antigen specific.

Lolly, I'll be interested in what the experts say.
Al

Thanks Al, it is starting to make sense to me now....I printed out Christine's post to take with me next week, and yes, it will be verrrrrry interesting to see what they have to add.

<3,
Lolly

Well, I forgot to take the printed abstract with me, and and my memory just wasn't up to the task of reciting the content to get a translation. I spoke with one of the doctors about our curiosity, and she agreed to provide me with an interpretation if I e-mail the link to the Group, so I'll post the response as soon as I get one...

Al and Christine, I talked with one of the study doctors at my visit last week, and she confirmed what Al has deduced; there are multiple sites for the antibodies to bind to, and the vaccine is specific for several of those sites. The lab work is showing that the vaccine stimulates the immune system to develop additional antibodies, basically "educating" the immune system about HER2 immunity! Just what we want to hear!

<3,
Lolly