AZ Guide u Biomedicine

ALLOVECTIN-7 /
METASTATIC MELANOMA

  • Allovectin-7 contains a gene for the antigen HLA B7, which stimulates a potent immune response.
    Direct injection of the gene into tumours results in cell surface expression of HLA B7 protein which induces the immune system to destroy those cells.
  • Around 80% of melanoma patients have tumours which do not express the HLA B7 antigen (HLA B-); these are potential candidates for Allovectin-7 therapy. While the remaining 20%, (HLA B+) seems not to be susceptible to the treatment.
    There are however doubts about this theory.
  • Preliminary analysis shows that Allovectin-7 therapy (10 microg/injection for 6 injections) induced tumour shrinkage in 5 of 11 patients with melanoma, restricted to cutaneous or lymph nodes, and 3 of these patients had a partial response.
    In 16 patients with melanoma, spread to multiple internal organs, only 1 patients had a complete response [1997].

TELOMERE

  • The telomeres, ends of linear chromosomes, are special chromatin structures.
  • In mammalian cells, they consist of non-coding repeats of the sequence TTAGGG.
  • The demonstration that telomeres are shorter in somatic tissue from older than from younger individuals has been a important finding.
  • Children born with Hutchinson-Gilford progenia have short telomeres.
    In other ageing-genetics disorders, such as Werner’s syndrome and Down’s syndrome, cells lose telomeres at two to three times the rate in age-matched controls.
  • Telomeres do not progressively shorten in germline (non-somatic) tissue, because of the expression of a ribonucleoprotein enzyme, telomerase.
  • Telomerase binds to telomeric ends and then a reverse-transcriptase component synthesises de novo TTAGGG repeats.

TELOMERE & CANCER

Although telomerase may not be essential for

  • the initial formation of tumor-cell growth
  • the progression and long term growth of tumours,

the malignant human tumours are associated with activated telomerase.

Q

May the inhibition of telomerase be a novel form of cancer therapy ?

XENOTRANSPLANTATION

  • Xenotransplantation (Transplantation of animal cells or organs into people) has received a go-ahead from the FDA in 1998.
  • There will be a close monitoring of results, a national registry of recipients and an archive of tissue from patients and donor animals.
  • Concerns remain about the risks involved in such procedures.
  • The first implantation of foetal pig brain cells into a patient with epilepsy has been performed at Beth Israel Deaconess Medical Center in Boston (USA).
    Electrodes are inserted into the brain for determining where the seizures are originating. Following the foetal pig cells will be injected through the electrode.
    The implant will produce the anticonvulsant amino acid, GABA.
  • Clinical trial programs are ongoing using porcine cells to treat:
  • Huntington’s disease
  • Parkinson’s disease

A large randomised controlled trial in 36 patients with Parkinson’s is to be performed at the University of South Florida School of Medicine and Emory University in Atlanta.

  • Preliminary data on 12 patients have shown no major complications and some improvement in symptoms.

 

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