BB20023: DNA and disease
A) Immunotherapy:
Non-specific immunotherapy

BCG
 Cytokines

Cell therapy
Cancer therapy 2: Newer therapies
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 (www.els.net)
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 approaches Cristofanilli 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
OR
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 flawed version in the 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
METHODS OF VECTOR DELIVERY approach.
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 against selected cells or 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 ( www.els.net
)