The cytokines: The interferon family - Pharmaceutical Biotechnology: Concepts and Aapplications - page 228

bioassay. The production and medical uses of selected interferons are summarized in the sec-
tions below.

8.3.1 Production and medical uses of interferon- α

Clinical studies undertaken in the late 1970s with multicomponent, impure IFN-α preparations
clearly illustrated the therapeutic potential of such interferons as an anti-cancer agent. These stud-
ies found that IFN-α could induce regression of tumours in signifi cant numbers of patients suffer-
ing from breast cancer, certain lymphomas (malignant tumour of the lymph nodes) and multiple
myeloma (malignant disease of the bone marrow). The interferon preparations could also delay
recurrence of tumour growth after surgery in patients suffering from osteogenic sarcoma (cancer
of connective tissue involved in bone formation).
The fi rst recombinant interferon to become available for clinical studies was IFN-

2a, in 1980.
Shortly afterwards the genes coding for additional IFN-αs were cloned and expressed, allowing
additional clinical studies. The antiviral, anti-tumour and immunomodulatory properties of these
interferons assured their approval for a variety of medical uses. rhIFN-αs manufactured/marketed
by a number of companies (Table 8.8) are generally produced in E. coli .
Clinical trials have shown the recombinant interferons to be effective in the treatment of various
cancer types, with rhIFN-

α

2b both approved for treatment of hairy cell leukaemia. This
is a rare B-lymphocyte neoplasm for which few effective treatments were previously available.
Administration of the recombinant interferons promotes signifi cant regression of the cancer in up
to 90 per cent of patients.
Schering Plough's rhIFN-

α 2a and - α

2b (Intron A) was fi rst approved in the USA in 1986 for treatment
of hairy cell leukaemia, but is now approved for use in more than 50 countries for up to 16 indica-
tions (Table 8.9). The producer microorganism is E. coli , which harbours a cytoplasmic expression
vector (KMAC-43) containing the interferon gene. The gene product is expressed intracellulary.
Intron A manufacturing facilities are located in New Jersey and in Brinny, Co. Cork, Ireland.
Upstream processing (fermentation) and downstream processing (purifi cation and formulation)
are physically separated, by being undertaken in separate buildings. Fermentation is generally
undertaken in specially designed 42 000 l stainless steel vessels. After recovery of the product
from the cells, a number of chromatographic purifi cation steps are undertaken, essentially within

α

Table 8.9 Some of the indications (i.e. medical conditions) for which Intron A is
approved. Note that the vast majority are either forms of cancer or viral infections

Laryngeal papillomatosis a Hairy cell leukaemia

Renal cell carcinoma Mycosis fungoides b

Basal cell carcinoma Condyloma acuminata c

Malignant melanoma Chronic hepatitis B

AIDS-related Kaposi's sarcoma Hepatitis C

Multiple myeloma Chronic hepatitis D

Chronic myelogenous leukaemia Chronic hepatitis, non-A, non-B/C hepatitis

Non-Hodgkin's lymphoma

a Benign growths (papillomas) in the larynx.
b A fungal disease.
c Genital warts.