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Therapeutic Application of Monoclonal Antibodies

1. Monoclonal antibodies specific to a cell type, for example,    cancerous cell, can be linked with a toxin to form an immunotoxin conjugate.

The antibody component ensures specific binding with the target cell and the toxin attached will kill such cells. Endosperm of castor has two polypeptides-A (toxin peptide, ricin) and B (cell-binding polypeptide, lectin). Ricin, by an irreversible enzymatic action, modifies the larger ribosomal units, making them incapable of protein synthesis.

Examples are: a) Action of antibody-Ricin A conjugate, reduces protein synthesis in mouse B cell tumours

b) Radioactive I131, Y90, Cu67, Pb212, etc., are incorporated into tumour specific antibody for irradiation of tumour cells

c) Radiolabelled antibody, used in radio imaging to detect tumour cells

2. Monoclonal antibodies are used as an effective strategy to minimize the rejection of graft from other individuals (allografts).

Tissue and bone marrow expalnts are rejected through the mediation of T-lymphocyte. In order to minimize tissue-graft rejection, T cell present in the circulatory system of recipient are eliminated before the transplantation process, using T cell specific Mabs.

This treatment, however, temporarily abolishes the ability of the recipient to generate antibodies against any foreign antigen, including that of the graft.

Mab OKT 3 is the most widely used monoclonal antibody for the treatment of acute cases of rejection of kidney transplants

Mabs can be utilized to provide passive immunity against disease.

Here, antibodies are produced elsewhere and then introduced into the body of the individual to provide immunity against the concerned pothagon.

Mabs are also used to purify antigens specific to pathogens, which are used as vaccines.

Overall, Ad is the easiest viral vector from the manufacturing viewpoint, allowing the production of large quantities with titre and in relatively robust formulations. Nevertheless, Ad shares with other viral vectors the problem that first-generation vector preparations are contaminated with replication competent virus (RCV), which arises through recombination between viral sequences in the vector and in the chromosome of the producer cells. Many of the clinical studies giving encouraging signs of efficacy use Ad vectors.

The most advanced of these delivers the wild-type gene for the tumour suppressor P53 for induction of tumour –cell killing. A series of phase II studies is underway, testing this recombinant virus alone and in combination with chemotherapies for the local management of various cancers. The steps involved gene therapy are illustrated.

The expression profile with first generation. Ad vectors is not suitable for the long-term correction of chronic diseases but is adequate for direct cell killing, for most immunotherapy strategies and for some acute diseases. The first generation vectors have an insert –size limit of ~7.5kb.