Springer, Encyclopedic Reference Of Cancer (2001) Ocr 7.0 Lotb.pdf

6 ABC Transporter
els. So far, the recombinant AAV have shown
a high antitumor efficacy, which supports
the further development of this approach.
* Delivery of antiangiogenic factors. The efficacy
of ! angiogenesis inhibitors (e.g., endostatin
or angiostatin) to undermine tumor
neovascularization and cancer progression
has been demonstrated in many animal
models. However, this cancer therapy requires
that the inhibitors are chronically administered
as recombinant proteins, which
is usually associated with severe problems.
Therefore, AAV-2 vectors with their unique
ability to mediate sustained gene expression
might prove particularly useful for this type
of tumor therapy. In fact, recombinant AAV
delivering antiangiogenic factors are currently
being developed and tested.
* Development of tumor vaccines. The latest
antitumor approach involving AAV-2 vectors
focuses on the development of vaccines,
in particular targeting cervical tumors induced
by ! human papillomaviruses (HPV).
It has recently been proposed that such vaccines
consist partly of the E6/E7 and/or the
L1 structural gene of the high-risk papillomavirus
types 16 or 18, perhaps fused to
an additional gene to provide a protein adjuvant.
There is hope that following rAAVmediated
delivery of the chimeric gene
into target cells, the potential vaccine will
be expressed to stimulate a host immune response.
This should eventually result in protection
against HPV-induced tumor formation.
References
1. Schlehofer, JR (1993) The tumor suppressive
properties of adeno-associated viruses. Mutation
Research 305:303-313
2. Berns KI, Giraud C (1996) Biology of adeno-associated
virus. Current Topics in Microbiology and
Immunology 218:1-23
3. Shaughnessy E, Lu D, Chatterjee S, Wong KK
(1996) Parvoviral vectors for the gene therapy
of cancer. Seminars in Oncology 23:159-171
4. Grimm D, Kern A, Rittner K, Kleinschmidt JA
(1998) Novel tools for production and purification
of recombinant adeno-associated virus vectors.
Human Gene Therapy 9:2745-2760
5. Grimm D, Kleinschmidt JA (1999) Progress in
adeno-associated virus type 2 vector production:
promises and prospects for clinical use. Human
Gene Therapy 10:2445-2450
ABC Transporter
Definition
ABC transporters are a superfamily of prokaryotic
and eukaryotic proteins. They are usually
involved in membrane transport and share a
homologous nucleotide-binding domain, ABC
(ATP-binding cassette). In addition to the
ABC domain, ABC transporters contain or interact
with hydrophobic domains containing
multiple transmembrane segments. Examples
of mammalian ABC transporters include
! P-glycoprotein, MRP (! multidrug-resistance
protein), cystic fibrosis transmembrane conductance
regulator (CFTR) and the transporter associated
with antigen processing (TAP).
ABL
Definition
The ABL gene encodes a nuclear tyrosine kinase
that is involved in chromosomal translocations
in ! CML.
Accelerated Senescence
Definition
Accelerated senescence, the process of rapid
terminal growth arrest, is accompanied by phenotypic
features of cell ! senescence (enlarged
and flattened morphology, increased granularity,
expression of specific biochemical and enzymatic
markers such as senescence-associated bgalactosidase
activity). It can be induced in normal
cells by DNA damage or introduction of mutant
! RAS and is also induced in tumor cells by
different anticancer drugs or ionizing radiation.