Antibodies Against Antibodies? Anti-Idiotype mAb Discovery

Myeloid-derived suppressor cells (MDSCs) play a critical role in the tumor microenvironment, contributing to immune evasion and resistance to checkpoint inhibitors. The leukocyte immunoglobulin-like receptor B2 (LILRB2), an immune checkpoint receptor expressed on myeloid cells, has emerged as a potential target for novel immunotherapies.

Utilizing PentaMice® technology, a diverse panel of monoclonal antibodies (mAbs) against LILRB2 was generated, screened, and characterized through advanced analytical techniques, including surface plasmon resonance and flow cytometry. Two lead humanized mAbs, hu6-I11A-IgG4 and hu4-O19A-IgG4, demonstrated high-affinity binding to LILRB2, with one also recognizing LILRB4. Functional assays in human MDSC-T cell co-cultures revealed their ability to reverse cytokine suppression, modulating key immune signaling pathways.

These findings highlight the therapeutic potential of targeting LILRB2/LILRB4 in cancer immunotherapy and suggest a new avenue for enhancing anti-tumor immune responses. Further exploration of these candidates may unlock new strategies for overcoming immune suppression in oncology.