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Chimeric receptor molecules with innate receptors for immunotherapy

antitumor activityHematological tumorsImmunotherapySolid tumors

Introduction

Adoptive therapy with Fcg-CR expressing lymphocytes. Fcg-CR are designed to redirect T cell functions against opsonized target cells. This is allowed by the presence of an extracellular Fcg-CR module of the chimeric receptor capable of binding monoclonal antibodies and of transductional signaling elements (CD28/z-chain) in its internal portion.

Technical features

The Fcg-CR encode for transmembrane chimeric proteins with dual function: a) they complex the Fc fragment of the IgG through the extracellular portion of the FcgRIII fragment of CD16 (CD16-CR); FcgRI of the CD64 (CD64-CR); FcgRIIb of the CD32 (CD32-CR); b) they activate the lytic machinery in effector cells of the immune system through the intracellular portions of CD28 and the z- chain present Fcg-CR. The mechanism of action involves the formation of a bridge between the “target cell” and the “reprogrammed T lymphocyte” mediated by monoclonal antibodies that recognize antigens present on the target cell. T lymphocytes transduced with The Fcg-CR improve the therapeutic efficacy of antibodies normally used in cancer therapies. Adoptive therapies with Fcg-CR lymphocytes can be optimized by administering monoclonal antibodies to multiple antigens, simultaneously or at different times of therapy.

Possible Applications

  • Oncological immunotherapy;
  • Infectious diseases;
  • Autoimmune Diseases.

Advantages

  • “Universal” chimeric receptors, designed to expand the immunotherapeutic options related to the use of antibodies;
  • Overcoming the resistance phenomena linked to the selection of antigen negative tumor cells;
  • Limitation of off-target toxicity thanks to the possibility to choose antibodies with appropriate affinity.