INVITADO: Dr. Norberto Zwirner, Instituto de Biología y Medicina Experimental (IBYME).
TÍTULO: “Immunotherapy beyond checkpoints: NKG2D ligands as targets for precision medicine”
FECHA: Lunes 21 de abril, 12:00 h.
LUGAR: Sala de Seminarios del IBioBA-CONICET-MPSP. Godoy Cruz 2390, C1425FQD, Buenos Aires, Argentina.
Abstract
The efficacy of immune checkpoint blockers (ICBs), such as anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies (mAbs), in cancer therapy remains suboptimal. Therefore, the identification and validation of novel targets, alongside the development of innovative therapeutic strategies to advance precision medicine, are critical for improving outcomes in cancer patients. MHC class I chain-related protein A (MICA) is a single-chain, membrane-bound protein encoded by a highly polymorphic gene within the MHC region. Its expression is largely restricted to both solid and hematological malignancies. MICA, along with its close homolog MICB, serves as a ligand for NKG2D, an activating receptor expressed on natural killer (NK) cells and cytotoxic CD8⁺ T cells. The interaction between MICA/B and NKG2D stimulates immune effector functions and supports tumor immunosurveillance. However, tumors can evade immune detection by shedding MICA/B, releasing soluble forms (sMICA/B) that impair NKG2D function and suppress NK and CD8⁺ T cell activity. Given the central role of NKG2D in immune activation, there is growing interest in targeting MICA and related ligands as novel approaches in immuno-oncology. This interest is further reinforced by the emerging role of NK cells in next-generation immunotherapies, particularly due to their capacity to mediate antibody-dependent cellular cytotoxicity (ADCC).
In this seminar, I will present data generated in our laboratory that supports the validation of MICA as a promising target for precision cancer immunotherapy. I will also describe the development of an anti-MICA mAb with therapeutic potential and discuss its competitive landscape. Finally, I will highlight key challenges encountered throughout the complex translational journey, from the obtention of a murine mAb to the development of a clinically viable therapeutic.