Erythrocyte-anti-PD1 conjugates in persons with advanced solid tumors resistant to anti-PD1/PDL1: preclinical characterization and results of a phase 1 trial - PubMed
2 days ago
- #PD1 blockade
- #erythrocyte conjugate
- #cancer immunotherapy
- Erythrocyte-anti-PD1 conjugates (αPD1-Ery) were developed to target PD1 antibodies to erythrocyte membranes.
- αPD1-Ery accumulates in the spleen, expanding effector T cells and reducing immunosuppressive myeloid cells.
- Preclinical studies showed tumor microenvironment reprogramming and suppressed tumor growth in mouse models.
- A phase 1 trial (NCT06026605) evaluated αPD1-Ery in 14 patients with advanced cancers resistant to prior anti-PD1/PDL1 therapy.
- No dose-limiting toxicities or severe adverse events (>grade 3) were observed.
- Objective response rate was 42.9% (1 complete, 5 partial responses); disease control rate was 78.6%.
- αPD1-Ery rapidly reduced circulating immunosuppressive myeloid cells, aligning with preclinical findings.
- The study met primary (safety) and secondary (efficacy, pharmacokinetics, etc.) endpoints.
- Spleen-targeted PD1 blockade via erythrocyte-antibody conjugates shows promise for cancer immunotherapy.