Immunoaugmenting therapeutics: Recombinant cytokines and biological response modifiers

Immunotherapy has a long history in the treatment of cancer. Immunoaugmenting drugs were popularized by William B. Coley, who treated cancer patients with mixed bacterial toxins early in the 20th century.1 These early studies resulted in the clinical approval of microbially derived substances such as Bacille Calmette-Guerin (BCG) (bladder cancer, USA), Krestin, Picibanil, and Lentinan (gastric and other cancers, Japan), and Biostim and Broncho-Vaxom (recurrent infections, Europe). While these “crude” drugs have numerous immune augmenting activities, they also have regulatory difficulties due to impurities, lot-to-lot variability, and adverse side effects. Similarly, traditional herbal medicines (Asia) may contain constituents with immunotherapeutic activity. The purification, characterization, and synthetic production of active moieties from natural products (Bestatin, Taxol) and culture supernatants (FK-506, Rapamycin, Deoxyspergualin, and Cyclosporin) have provided valuable drugs. The current developmental focus is on recombinant proteins (cytokines and monoclonal antibodies (mAbs)), although the utility of these drugs are limited due, in part, to bioactivity and pharmacologic deficiencies (see chapter 8 of this volume for a discussion of cytokines and monoclonal antibodies as therapeutic agents).