PMID- 18077530
OWN - NLM
STAT- MEDLINE
DCOM- 20080229
LR  - 20220318
IS  - 0161-5505 (Print)
IS  - 0161-5505 (Linking)
VI  - 49
IP  - 1
DP  - 2008 Jan
TI  - Multifunctional antibodies by the Dock-and-Lock method for improved cancer 
      imaging and therapy by pretargeting.
PG  - 158-63
AB  - The Dock-and-Lock (DNL) method, which makes bioactive molecules with multivalency 
      and multifunctionality, is a new approach to develop targeting molecules for 
      improved cancer imaging and therapy. It involves the use of a pair of distinct 
      protein domains involved in the natural association between cyclic adenosine 
      monophosphate (cAMP)-dependent protein kinase A (PKA) and A-kinase anchoring 
      proteins (AKAPs). The dimerization and docking domain found in the regulatory 
      subunit of PKA and the anchoring domain (AD) of an interactive AKAP are each 
      attached to a biologic entity, and the resulting derivatives, when combined, 
      readily form a stably tethered complex of a defined composition that fully 
      retains the functions of the individual constituents. The DNL method has 
      generated several trivalent, bispecific, binding proteins, each consisting of 2 
      identical Fab fragments linked site-specifically to a different Fab fragment. For 
      example, 2 identical Fabs reacting with carcinoembryonic antigen (CEA) are bound 
      to a Fab reacting with a hapten peptide that bears a diagnostic or therapeutic 
      radionuclide. Using a 2-step, pretargeting method that separates the bivalent 
      anti-CEA antibody targeting of tumor from the delivery of the radioactive peptide 
      that is captured by the second Fab of the tri-Fab construct, an improved method 
      of cancer imaging and therapy has been developed and shows very sensitive and 
      specific targeting of CEA-expressing tumors for either diagnostic imaging, such 
      as with immunoSPECT and immunoPET, or radioimmunotherapy. Improved therapeutic 
      efficacy is shown with pretargeting in a pancreatic cancer xenograft model given 
      a tri-Fab to a pancreatic cancer MUC1 and the hapten peptide labeled with (90)Y.
FAU - Goldenberg, David M
AU  - Goldenberg DM
AD  - Garden State Cancer Center, Center for Molecular Medicine and Immunology, 
      Belleville, New Jersey 07109, USA. dmg.gscancer@att.net
FAU - Rossi, Edmund A
AU  - Rossi EA
FAU - Sharkey, Robert M
AU  - Sharkey RM
FAU - McBride, William J
AU  - McBride WJ
FAU - Chang, Chien-Hsing
AU  - Chang CH
LA  - eng
GR  - P01 CA10395/CA/NCI NIH HHS/United States
GR  - R01 CA107088/CA/NCI NIH HHS/United States
GR  - R01 CA115755/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20071212
PL  - United States
TA  - J Nucl Med
JT  - Journal of nuclear medicine : official publication, Society of Nuclear Medicine
JID - 0217410
RN  - 0 (A Kinase Anchor Proteins)
RN  - 0 (Antibodies, Bispecific)
RN  - 0 (Immunoglobulin Fab Fragments)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - A Kinase Anchor Proteins/chemistry
MH  - Animals
MH  - Antibodies, Bispecific/chemistry/*therapeutic use
MH  - Colonic Neoplasms/diagnostic imaging/drug therapy/immunology
MH  - Cyclic AMP-Dependent Protein Kinases/chemistry
MH  - Immunoglobulin Fab Fragments/chemistry
MH  - Lung Neoplasms/diagnostic imaging/drug therapy/immunology
MH  - Mice
MH  - Neoplasm Transplantation
MH  - Pancreatic Neoplasms/diagnostic imaging/drug therapy/immunology
MH  - Positron-Emission Tomography
MH  - Protein Structure, Tertiary
MH  - Radioimmunotherapy
MH  - Transplantation, Heterologous
RF  - 43
EDAT- 2007/12/14 09:00
MHDA- 2008/03/01 09:00
CRDT- 2007/12/14 09:00
PHST- 2007/12/14 09:00 [pubmed]
PHST- 2008/03/01 09:00 [medline]
PHST- 2007/12/14 09:00 [entrez]
AID - jnumed.107.046185 [pii]
AID - 10.2967/jnumed.107.046185 [doi]
PST - ppublish
SO  - J Nucl Med. 2008 Jan;49(1):158-63. doi: 10.2967/jnumed.107.046185. Epub 2007 Dec 
      12.