Monoclonal antibodies used in oncology exert direct anti-tumor action leading to cancer cell death. This is due to a variety of mechanisms, ranging from the induction of apoptosis to the recruitment of effector cells from the innate immunity. However, antibodies can also induce long-lasting anti-tumor effects thanks to the induction of an adaptive immunity where CD4(+) and CD8(+) T cells play a central role. Different preclinical experimental models, strengthened by a few clinical observations, have shown that, far from being involved only in passive immunotherapy, monoclonal antibodies used in oncology are also endowed with a "vaccine" effect, inducing immune memory, likely responsible for the long-lasting clinical responses that have been sometimes observed. This capacity of triggering/re-installing tumor immune surveillance could be also reinforced by the use, possibly in combination, of antibodies antagonizing molecules such as CTLA-4 or PD-1 that play a key role in the inhibition of the anti-tumor immune responses. Finally, this novel paradigm of therapeutic anti-tumor antibodies as inducers of anti-tumor adaptive immune responses with long-term memory should lead us to re-examine how antibody treatment, chemotherapy, radiotherapy, and biological response modifiers are combined, in particular both in terms of timing and doses.
Med Sci (Paris)
57 - 63
Adaptive Immunity, Antibodies, Monoclonal, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cancer Vaccines, Humans, Immunization, Passive, Neoplasms, Vaccination