Cancer therapy I ( lecture 17)

BB20023: DNA and disease
Cancer therapy 2: Newer therapies
A) Immunotherapy:
Non-specific immunotherapy
 Cytokines
 Cell therapy
Specific immunotherapy
I) adoptive
Antibody therapy
Adoptive transfer of T cells
II) Vaccination
Tumour-based vaccines
Virus-based vaccines
Peptide-based vaccines
BB20023: DNA and disease
Immuno reading
1) Tumours: Immunotherapy by Mark P Rubinstein and David J Cole (
2) Immunotherapy for cancer by L.J Old Scientific American (Sept 1996) special issue , pg 102
3) Progress on new vaccine strategies for the immunotherapy and prevention of cancer by Jay A.
Berzofsky, et al The Journal of Clinical Investigation Volume 113 Number 11 June 2004 1515-1525
B) ANGIOTHERAPY:Angioreading:
1) Fighting cancer by attacking its blood supply by
J Folkman Scientific American (Sept 1996) sp
issue pg 116
2) Angiogenesis modulation in cancer research:
Novel clinical approachesCristofanilli M,
Charnsangavej C, Hortobagyi GN;
C) GENE THERAPY: 2 main ways
a) Antisense therapy (suppress gene expression
b) Gene augmentation (supplement defective gene)
a) Anti-sense therapy: compensates for genetic mutations that
produce destructive proteins. The main strategies involved are
1) short stretches of synthetic DNA that target the mRNA
transcripts of abnormal proteins preventing its translation
2) small RNA molecules (siRNA) used to degrade aberrant
RNA transcripts
3) provide a gene for a protein (intracellular antibody) that can
block the activity of the mutant protein
4) design hybrids of DNA / RNA that might direct repair of the
mutant gene
BB20023: DNA and disease
b) Gene augmentation (supplement defective gene)
In theory, a targeted gene is
delivered to a cell so that it
physically takes the place of that
chromosome. In practice, most
therapies simply add a useful gene
into a selected cell type to
compensate for the missing or
flawed version or even instil an
entirely new version. Most
anticancer therapies take the latter
A direct approach is by inducing
cancer cells to make a protein that
will kill the cell.
An indirect approach is by
stimulating an immune response
eliminating the blood supply.
Vectors: Carrier molecules designed specifically to enter cells & deposit therapeutic genes. Vectors can be
viral or non-viral.
Viral vectors include
Retrovirus: Replication & virulence genes can be substituted with therapeutic genes (should help transfer
but not create disease). It is ideally targeted for haemopoietic stem cells.
Problems of retroviral therapy include
Lack of cell specificity: Promiscuous depositing genes into several cell types resulting in reduced
targeting efficiency and unwanted physiological effects
Random splicing into host DNA resulting in normal gene disruption and/or alteration in gene function
Adenoviruses: do not insert into genome , temporary & lack of specificity with strong immune response
Adenoassociated virus: Integrate into genome but small in size. E.g herpes or pox viruses
Non viral vectors include
liposomes (lipoplexes): lack of specificity
amino acid polymers
naked DNA
artificial human chromosomes
Gene therapy reading:
1) Human gene therapy by Ioannou, Panos A (
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