Palettes of vaccines and immunostimulatory monoclonal antibodies for combination

Abstract

Various monoclonal antibodies (mAb) target immune system molecules to enhance immunity by costimulating T cells (i.e., CD137, OX40, CD40, GITR) or interfering in coinhibitory signals (i.e., CTLA-4, PD-1). These powerful agents can be guided by cancer vaccines to enhance immunity against tumor but not self tissues. Clinically powerful therapeutic synergies are at hand.

Fig. 1

Strategies for immunotherapy combinations. Stepwise rationale approaches for combinations of immunostimulatory mAb and procedures of immunization against malignant antigens. Mouse experimentation provides a recipe for clinicians: First, use procedures that enhance the number of primed nonanergic T cells in the organism by means of vaccines, adoptive transfer, or procedures to enhance the immunogenicity of a tumor lesion. Then apply strategies to de-repress or stimulate artificially the ongoing immune response, for the most part considering immunostimulatory mAb. The optimal interval between immunization procedures and the further immunostimulatory treatment may vary. Therapies involving various elements have made a difference in AIDS, tuberculosis, and chemotherapy for certain malignancies. In cancer immunotherapy, no single action is expected to reach dramatic efficacy in human patients but it is likely that L’union fait la force.