Recent Progress in Polymer Therapeutics as Nanomedicines - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 99

Another example is the PEG-antibody fragment angiogenesis
inhibitor (CDP791) which is now in phase II clinical study in
combination with carboplatin and paclitaxel chemotherapy in
first-line non-small cell lung cancer (NSCLC) [127].
(ii) Interferons (IFNs) are multifunctional regulatory cytokines
involved in the control of cell function and replication.
PEGylation of IFN delays its clearance and reduces its
immunogenicity [128]. In addition, two PEG-interferon- α
conjugates, IFN- α -2a (PEGASYS ® ) and IFN- α -2b (PEG-
INTRON ® ), have been approved as treatments for hepatitis B
and C [129]. These days, several clinical studies are evaluating
the eff ectiveness of PEG-INTRON ® as adjuvant therapy in
certain anticancer protocols. This conjugate is now in phase II
study for resected stage III melanoma. In the case of PEGASYS ® ,
the coupling of IFN- α -2a to a branched PEG 40 kDa enables
the prolongation of the in vivo half-life, although a reduction
in the in vitro activity occurs. This conjugate serves as a good
example for the benefits and limits of PEGylation [15].
(iii) PEG 20 kDa conjugated to the granulocyte colony stimulating
factor (G-CSF) showed an improved pharmacokinetic profile
as consequence to reduced kidney excretion. The PEG-G-CSF
conjugate (Neulasta ® ) was approved for human use in 2002
for the treatment of febrile neutropenia [130].
(iv) Delivering depleting enzymes to the tumor area will cause to
degradation of essential amino acids, and eventually to the
inhibition of the tumor growth. PEG-asparaginase (Oncaspar ® )
was the first anti-tumor PEGylated conjugate/enzyme to be
approved for clinical use in 1994 as treatment of patients
with lymphoblastic leukaemia (ALL). Asparaginase converts
asparagine into aspartate and ammonia, thus can treat cancer
cells, which rely on the serum supply of asparagine, like the
leukemic lymphoblasts cells. This approach of amino acid
depleting anti-cancer therapy yielded additional PEG-enzyme
conjugates, which are presently under clinical trials [15]. A
diff erent example is the PEG-adenosine deaminase, which
was the first PEGylated protein to enter the market in 1990. It
is used to treat adenosine deaminase deficient X-linked severe
combined immunodeficiency disease (SCID)[131].
PEGylation is a mature and eff ective delivery technology for
improving the therapeutic index of proteins. The growing interest