Pharmacological intervention on the immune system to
achieve more intense lymphocyte responses has potential application
in tumour immunology and in the treatment of chronic
viral diseases. Immunostimulating monoclonal antibodies are
defined as a new family of drugs that augment cellular immune
responses. They interact as artificial ligands with functional proteins
of the immune system, either activating or inhibiting their
functions. There are humanized monoclonal antibodies directed
to the inhibitory receptor CD152 (CTLA-4) that are being tested
in clinical trials with evidence of antitumoural activity. As a
drawback, anti-CTLA-4 monoclonal antibodies induce severe
autoimmunity reactions in a fraction of the patients. Anti-CD137
monoclonal antibodies have the ability to induce potent
immune responses mainly mediated by cytotoxic lymphocytes
with the result of frequent complete tumour eradications in
mice. Comparative studies in experimental models indicate that
the antitumour activity of anti-CD137 monoclonal antibodies is
superior to that of anti-CD152. CD137 (4-1BB) is a leukocyte differentiation
antigen selectively expressed on the surface of activated
T and NK lymphocytes, as well as on dendritic cells. Monoclonal
antibodies acting as artificial stimulatory ligands of this
receptor (anti-CD137 agonist antibodies) enhance cellular antitumoural
and antiviral immunity in a variety of mouse models.
Paradoxically, anti-CD137 monoclonal antibodies are therapeutic
or preventive in the course of model autoimmune diseases in
mice. In light of these experimental results, a number of
research groups have humanized antibodies against human
CD137 and early clinical trials are about to start
