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Immunoconjugate Anticancer Therapeutics

  • Serengulam V. Govindan
  • David M. Goldenberg
Chapter
Part of the Macromolecular Anticancer Therapeutics book series (CDD&D)

Abstract

Immunoconjugate therapy has entered the mainstream of cancer management with the regulatory approval and the bench to bedside transition of three antibody conjugates for lymphoma and leukemia. A number of antibody conjugates of radionuclides, drugs, and protein toxins are in various stages of clinical development. These treatments are relatively more effective in hematological cancers than in solid cancers and are generally more effective in minimal disease, in the adjuvant setting, and as combination therapies with nonoverlapping toxicities. Pretargeted radioimmunotherapy, with its superiority to direct radioimmunotherapy documented in preclinical studies, is being actively pursued to improve efficacy and minimize toxicity. Emerging approaches to the design of conjugates with defined structure and stoichiometry provide opportunities to expand the therapeutic window. In this category, the “dock-and-lock” (DNL) technology enables the facile assembly of multifunctional structures of defined composition, combining the targeting and the therapeutic moieties site specifically. Recent advances in the use of different classes of immunoconjugates are described.

Keywords

Autologous Stem Cell Transplantation Anaplastic Large Cell Lymphoma Gemtuzumab Ozogamicin Pokeweed Antiviral Protein Anchor Domain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

AA

anaplastic astrocytoma

AD

anchoring domain

AML

acute myeloid leukemia

AO

anaplastic oligodendroglioma

DDD

dimerization and docking domain

DNL

“dock-and-lock”

DOTA

1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid

DT

diphtheria toxin

DTPA

diethylenetriaminepentaacetic acid

GBM

glioblastoma multiforme

GO

gemtuzumab ozogamicin

HSG

histamine-succinyl-glycine

IgG

immunoglobulinG

mAbs

monoclonal antibodies

MMAE

maytansine and monomethyl auristatin E

MTC

medullary thyroid cancer

MTD

maximum-tolerated dose

NHL

non-Hodgkin’s lymphoma

OS

overall survival

PE

Pseudomonas exotoxin

PFS

progression-free survival

ASCT

autologous stem cell transplantation

RAIT

radioimmunotherapy

r-chemo

rituximab-chemotherapy combination

RNase

ribonucleases

SPECT

single photon emission computed tomography

TBI

Total-body irradiation

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Immunomedics, Inc.Morris PlainsUSA
  2. 2.Garden State Cancer Center at the Center for Molecular Medicine and ImmunologyBellevilleUSA

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