3. Custom-made antibodies

Most of the antibodies are produced by generating stably transformed plants that express the protein. For the development of an idiotype vaccine another approach has been used. A tobacco mosaic tobamovirus (TMV) based vector has been developed for the production of a secreted ScFv protein during virus infection of non-transgenic tobacco plants. In this vector a virus promoter regulates the expression of the ScFv gene and the antibody coding sequence is inserted downstream from a rice α-amylase leader sequence, which target the protein to the extracellular compartment of the plant (Figure 41.3).

This antibody produced can be used for the treatment of B-cell lymphoma. In this disease, these cells produce a particular antibody that is unique to each patient. In this idiotype vaccine system the patient is treated with a copy of the lymphoma antibody to generate immunity against the original antibody producing lymphoma cells. Each individual antibody has a variable region that has a unique antigenic constitution, the idiotype. Thus, the idiotype vaccine will only raise a specific response against the lymphoma cells and not against other cells. Using a TMV vector system, it is now possible to generate the idiotype region of a tumor specific immunoglobulin as a ScFv. The system was first developed using mice as model, but it has now entered clinical trials. It is interesting that each of the antibodies in the clinical trials is unique, and can be considered as a single drug.

The advantage of this transient expression system is that it is very rapid and can be used to produce small batches of customized antibody. Another advantage is that it is possible to harvest enough material for clinical use from green house grown plants, thus ensuring high levels of containment.

Figure 41.3: The engineered TMV vector for the expression of pharmaceutical proteins
TsP-translation start position; TcP-tomato coat proteins; pBR322- bacteria replication sequence