(M1030-03-13) Cationic Peptide Anchor-Mediated Binding to Tumor Extracellular Matrix Improves Intratumoral Retention of Agonist CD40 Antibody

Purpose: Intratumoral delivery of immunotherapy has gained increased attention for its potential to enhance tumor exposure and antitumor efficacy compared to systemic delivery. However, intratumoral performance after injection remains poorly defined, and a rational design of tumor-localized immunotherapy can be developed to improve the performance of local immunotherapy.

Methods: Here, taking advantage of the acidic nature of the tumor microenvironment, we conjugated our rationally designed cationic peptides to agonist CD40 antibody to improve its intratumoral performance.

Results: We find that cationic peptide conjugated CD40 increased binding to tumor-like extracellular matrix and following intratumoral injection, prolonged its retention within pancreatic tumors derived from the KPC mouse model, as compared to the unconjugated CD40 antibody. By submerging tumor tissue in the bath of fluorescently-labeled CD40 antibody, we observed an enhanced uptake of cationic peptide conjugated CD40 within tumor tissues.

Conclusion: Thus, employing cationic peptides as anchors represents a promising modular delivery approach to enhance tumor exposure of immunotherapy, achieving improved antitumor efficacy.


Figure . Binding to recombinant mouse CD40 and tumor-like ECM.