David:
This is one where you want to let IR at DNDN do all of the work for you (and for Peter and me).
Ask them how this project differs from the one at Idec about 10 years ago, why myeloma differs from lymphoma, etc.
Don't get me wrong..... the trial does differ. I am not trying to imply anything other than that the project is a new wrinkle on an old concept.
They appear to be avoiding the word "idiotype", when in fact they are trying to immunize against clonally-determined immunoglobulin antigens (idiotypes). Ask them why somatic mutation won't kill this project as it did earlier efforts. A name at Stanford is Rich Levy (see below), but **again**, the DNDN project is an improvement on the old theme.
You might also ask if a competitive project at Vical, using patient-specific DNA vaccines, is still conceptually alive. If so, what will happen to mylovenge in the long-term competitive picture?
Every biotech investor should read Nature Biotechnology, from the first day it was published.
Rick
Blood 1997 May 1;89(9):3129-35
Tumor-specific idiotype vaccines in the treatment of patients with B-cell
lymphoma--long-term results of a clinical trial.
Hsu FJ, Caspar CB, Czerwinski D, Kwak LW, Liles TM, Syrengelas A,
Taidi-Laskowski B, Levy R
Division of Oncology, Stanford University Medical Center, CA 94305, USA.
The surface Ig on each B-cell lymphoma has unique portions (idiotypes), which can be
recognized by the immune system. In this study, we immunized patients against the Ig expressed
by their tumor and observed their clinical outcomes. After standard chemotherapy, 41 patients
with non-Hodgkin's B-cell lymphoma received a series of injections with a vaccine consisting of
tumor Ig protein coupled to keyhole limpet hemocyanin and emulsified in an immunologic
adjuvant. Subjects were observed for toxicity, immune responses, and tumor status. The median
duration of follow-up of all patients is 7.3 years from diagnosis and 5.3 years from the last
chemotherapy given before vaccine treatment. Twenty patients (49%) generated specific immune
responses against the idiotypes of their tumor Ig. Two patients who had residual disease
experienced complete tumor regression in association with the development of these immune
responses. The median duration of freedom from disease progression and overall survival of all
20 patients mounting an anti-idiotype immune response are significantly prolonged compared to
the patients who did not mount an immune response. Thirty-two patients were in their first
remission and nine were in subsequent remissions before beginning vaccine treatments. Analysis
of the 32 first remission patients also shows an improved clinical outcome for those patients who
mounted a specific immune response compared to those who did not (freedom from progression,
7.9 years v 1.3 years P = .0001; median survival from time of last chemotherapy not yet reached
v 7 years, P = .04). This study confirms an earlier report that patients with B-cell lymphoma can
be induced to make a specific immune response against the Ig expressed by their own tumor. It
further shows that the ability to make such an immune response is correlated with a more
favorable clinical outcome. Prospective controlled trials will be needed to prove a causal
relationship between anti-idiotype immunity and improved clinical outcome. |
