Introduction

There are two pressing reasons for producing large quantities of monoclonal antibodies by in vitro technologies. The first is associated with the problems of the presently popular alternative route: that of using mice and rats to produce ascites fluids from the inherently carcinogenic effects of inoculating them with a monoclonal antibody-producing hybridoma. This route has five major problems:

1. (i) it is costly in manpower and facilities;

2. (ii) the materials produced, although present in high concentration (2–10 mg/ml) are contaminated with other immunoglobulins, plasma proteins (70–80%) and other possibly infectious adventitious agents;

3. (iii) there is a growing movement in modern societies to cause the minimum discomfort to those animals which are of value nutritionally, scientifically and technically;

4. (iv) there is a lack of reproducibility; and

5. (v) it is not possible to produce human antibodies in rodent bodies.

The more positive reasons for looking towards in vitro technologies are:

1. (i) the ability to scale up such cultures and thus to be able to satisfy requirements for kilogram or hundred to thousand kilogram (1,2) quantities of pure antibody for a variety of therapeutic and preparative purposes; and

2. (ii) the exploitation of the potential of animal cell systems for the more efficient production of antibodies by using very dense suspensions of animals cells.

The difference between the rodent and tank methods can be illustrated by presenting the alternative systems necessary to produce 1 kg of antibody (Table 5.1). The size of the tank culture for such a production (5000 1) is well within current practice for animal cell cultures; lymphoblastoid interferon is presently produced commercially from mammalian cells in 8000 1 volumes (3, 4).