Biology subjects

Lim, S.-O.

Publications and source records attributed to Lim, S.-O..

2 recordsLinked to original sources

bioRxiv2025

CD40 agonistic-monovalent streptavidin fusion antibody for targeted neoantigen peptide delivery and potent cancer vaccination

Cancer vaccines targeting patient-derived neoantigens offer great promise for personalized cancer therapy but face challenges in achieving targeted delivery to antigen-presenting cells (APCs) to elicit robust and durable cancer-specific immune responses. We synthesized an anti-mouse CD40 agonistic-monovalent streptavidin fusion antibody (CD40-mSAs), which enables targeted delivery of biotinylated neoantigen peptides to APCs in draining lymph nodes (dLNs). We confirmed mSA expression on the engineered antibody and its strong binding affinities to mouse CD40 and biotin. Advanced microscopy demonstrated that CD40-mSAs enhances homing to dLNs and intracellular delivery of neoantigen peptides to critical APC subsets, such as cDC1. The potent agonistic effects of CD40-mSAs on dendritic cell maturation, activation, and antigen presentation were verified through in vitro assays. Vaccination with CD40-mSAs elicited robust cancer-specific CD8 T cell responses, leading to significant tumor regression and prevention in a mouse tumor model. These results support CD40-mSAs as an all-in-one vaccine delivery platform with multifunctional immunopharmacological advantages and strong translational potential for personalized cancer vaccination. TeaserCD40-mSAs is an engineered anti-CD40 agonistic antibody designed to enhance cancer vaccine delivery.

immunology↗

bioRxiv2023

Tumor cell-derived lactic acid inhibits the interaction of PD-L1 protein and PD-L1 antibody in the PD-L1/PD-1 blockade therapy-resistant tumor

Immune checkpoint blockade therapy targeting the PD-1/PD-L1 axis has shown remarkable clinical impact in multiple cancer types. Nontheless, despite the recent success of PD-1/PD-L1 blockade therapy, such response rates in cancer patients have been limited to tumors encompassing specific tumor microenvironment characteristics. The altered metabolic activity of cancer cells shapes the anti-tumor immune response by affecting the activity of immune cells. However, it remains mostly unknown how the altered metabolic activity of cancer cells impacts their resistance to PD-1/PD-L1 blockade therapy. Here we found that tumor cell-derived lactic acid renders the immunosuppressive tumor microenvironment in the PD-1/PD-L1 blockade-resistant tumors by inhibiting the interaction between the PD-L1 protein and anti-PD-L1 antibody. Furthermore, we showed that the combination therapy of targeting PD-L1 with our PD-L1 antibody-drug conjugate (PD-L1-ADC) and reducing lactic acid with the MCT-1 inhibitor, AZD3965, can effectively treat the PD-1/PD-L1 blockade resistant tumors. The findings in this study provide a new mechanism of how lactic acid induces an immunosuppressive environment and suggest a potential combination treatment to overcome the PD-1/PD-L1 blockade therapy resistance.

cancer biology↗