Back to the Top
The following message was posted to: PharmPK
I work as a scientist in a biotech company, Arius Research Inc.,
where we are trying to develop monoclonal antibodies as therapeutic
agents for cancer treatment, particularly of solid tumors. However we
are focusing on the development of naked antibodies and not on their
use as carriers of a pro-drug, although some of the antibodies in our
current pipeline may actually have the potential for that use.
I am trying to get information on the pharmacodynamics and
pharmacokinetics of monoclonal antibodies and in understanding how
the side effects of their use as naked therapeutics agents relate
with the normal distribution of the target antigen. Although side
effects have been observed I cannot find anywhere a detailed
investigation of the mechanisms responsible for the side effects.
Ideally the naked antibody would recognize an antigen only expressed
during the disease state. However that is not the case, and even the
MAbs that have been approved by the FDA for use as anti-cancer
therapeutics recognize antigens that are expressed in a non-disease
individual, although they may, or may not, be over-expressed during
tumor progression.
Therefore my concern about the relation between the side effects and
normal antigen distribution. Certainly some side effects may be due
to the elimination of the tumor cells but others will be related with
recognition of the normally expressed antigen. Therefore I am trying
to obtain information also on how do antibodies distribute upon
administration and whether during the therapy they have the
possibility of binding to the normally present antigen if the latter
is expressed in not just in cells of the vascular system but also in
other tissues.
I would very much appreciate feedback from anyone who has had first
hand experience in this type of studies.
Luis
Luis A. G. da Cruz, Ph.D.
Senior Scientist, Biochemistry Department
Arius Research Inc.
55 York Street, 16th floor
Toronto, Ontario
M5J 1R7
phone: 416.862.2323 ext.237
email: ldacruz.aaa.ariusresearch.com
fax: 416.862.9696
www.ariusresearch.com
Back to the Top
The following message was posted to: PharmPK
Dear Luis,
As you correctly stated there are no tumor-specific antigens that is
why we say tumor-associated antigen.
Do you have a target organ for toxicity identified during Tox studies?
Do you have the radiolabelled Moab?
Have you conducted tissue distribution and autoradiography studies
using the radiolabelled Moab?
These studies will give you an idea of the organ/s where the Moab
distributes.
You could then perform histology and staining (immunostaining) with
anti-Moab second antibodies. Your pathologist will tell you if there
is tissue damage where high staining occurs and what kind of cellular/
tissue alterations are produced by localization of the Moab.
Be aware that even if a particular organ express the antigen against
which you Moab is directed, this does not mean that the antigen is
accessible by the Moab. That is why immunostaining of tissue slices
is very informative.
See for some details:
Cancer Immunol Immunother. 1992;35(4):251-6.
Targeted Diagn Ther. 1990;3:289-304. Review
Cancer Immunol Immunother. 1989;29(3):167-70.
Best regards,
Stefano
Stefano Persiani, PhD
Director,
Drug Metabolism and Pharmacokinetics
Clinical Pharmacology Department
Rotta Research Laboratorium
The R&D Division of Rottapharm SpA
Via Valosa di Sopra, 9
20052 Monza (MI)
ITALY
T +39 039 7390396
F +39 039 7390371
C +335 7840850
E-mail: stefano.persiani.-at-.rotta.com
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)