Nanoantibodies as Therapeutics and Diagnostics
Background:
The National Cancer Institute
Center for Cancer Research Nanobiology Program is seeking
statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or
commercialize nanoantibodies as therapeutics or diagnostics.
The size and stability of antibodies used for diagnosis and therapy
of diseases are critical for their efficacy. Small binding entities
based on the heavy chain variable domain (VH) have been
developed from humans, but some may be unstable because they have
evolved to interact with the light chain variable domain
(VL). Single domain antibodies from Camelid (nanobodies)
are stable (naturally occurring as part of a heavy chain only
antibody) but could be immunogenic in humans because are foreign
proteins.
Technology:
This invention involves
conceptually novel scaffolds based on human antibody constant
domains in contrast to those described previously which are based
on the antibody variable domains. In the naturally occurring full
size antibodies the CH2 domains (CH3 for IgE and IgM) are only
weakly interacting through carbohydrates; thus the CH2 domain could
be appropriate scaffold for engineering human antibodies. These
antibody domains can also confer some effector functions. The
engineered CH2 domains (nanoantibodies) are highly soluble, very
stable, monomeric, and can be expressed at high levels. The small
size of the nanoantibodies ensures efficient penetration into solid
tumors and lymphoid tissues where HIV replicates as well as
increased efficacy against HIV and other viruses that are able to
avoid neutralization by larger, naturally occurring antibodies. In
addition to HIV and other infectious and immune diseases, this
technology can be used to develop diagnostics and therapeutics for
numerous diseases including cancer. Because these nanoantibodies
are derived from human sequences, they are likely to have lower
toxic and immunogenic effects.
Further R&D
Needed:
- Testing of nanoantibodies for functional activity in animal
models
- Conjugation of nanoliposomes and small molecule drugs to
nanoantibodies
R&D Status: Proof
of concept experiments has been completed.
IP Status: U.S.
Provisional Application No. 61/063,245 filed 31 Jan 2008
Value Proposition
Solution:
- Might produce small nanoantibodies that are effective against
viruses unable to be neutralized by larger antibodies
- Development of stable, soluble, antibodies with lower toxic and
immunogenic effects
- Ability to create high-affinity binders to many antigens of
interest
- Potential for diagnosis and treatment of HIV, cancer, and
numerous other diseases
Contact
Information:
John D. Hewes, Ph.D., NCI
Technology Transfer Center
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov
Reference: #644 JH
Posted 04/09/2008
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