Therapeutic anti-tumor vaccines: from tumor inhibition to enhancement.

PAULA CHIARELLA; VERONICA REFFO; JUAN BRUZZO; OSCAR D. BUSTUOABAD; RAÚL A. RUGGIERO

Clinical Medicine Insights: Oncology

Libertas Academicas

Lugar: Auckland; Año: 2008 vol. 2 p. 237 - 245

1179-5549

Numerous immunization trials aimed to prevent the growth of experimental animal tumors and human hepatocarcinomas induced by hepatitis B virus proved to be successful. These promissory results prompted researchers and physicians to use vaccines in a therapeutic mode. However, most of the attempts to cause an immunologically-mediated regression of animal and human established tumors larger than a minimal critical size have been disappointing even when strongly immunogenic murine tumors were concerned. The most simple interpretation for this fact is would be that the number of immune-reactants that are generated by a given vaccine is enough to efficiently deal with a small number of tumor cells such as that present in a small tumor inoculum or in an incipient tumor but not with a larger one present in a larger growing tumor. However, data from this work suggest thst immunotherapy against established tumors or against residual tumor cells after debulking the primary tumor, can render not only inhibitory or null but also stimulatory effects on tumor growth, depending upon where in the immune response curve, relating the quantity of the immune response to the quantity of target tumor cells, the system is located, with high ratios rendering tumor inhibition, medium an very low ratios rendering null effects an low ratios - between medium and very low ones – rendering tumor stimulation. Since the magnitude of these ratios would depend on the antigenic profile of the tumor, the immunogenic strength of the vaccine used and the immunological state of the host, studies aimed to determine in each particular case, the magnitude of these variables, seem to be necessary as a pre-condition to design rational immunotherapeutic approaches to cancer that could optimize the effects of an active or passive immunological treatment changing a null or stimulatory ratio between immune-reactants and target cells, by an inhibitory one. In contrast, if these studies are neglected, the worst thing that an immunotherapist could expect is not merely a null effect but an acceleration of tumor growth and earlier death of its patients.