| First Author | Santollani L | Year | 2024 |
| Journal | Nat Immunol | Volume | 25 |
| Issue | 10 | Pages | 1820-1829 |
| PubMed ID | 39112631 | Mgi Jnum | J:361532 |
| Mgi Id | MGI:7856830 | Doi | 10.1038/s41590-024-01925-7 |
| Citation | Santollani L, et al. (2024) Local delivery of cell surface-targeted immunocytokines programs systemic antitumor immunity. Nat Immunol 25(10):1820-1829 |
| abstractText | Systemically administered cytokines are potent immunotherapeutics but can cause severe dose-limiting toxicities. To overcome this challenge, cytokines have been engineered for intratumoral retention after local delivery. However, despite inducing regression of treated lesions, tumor-localized cytokines often elicit only modest responses at distal untreated tumors. In the present study, we report a localized cytokine therapy that safely elicits systemic antitumor immunity by targeting the ubiquitous leukocyte receptor CD45. CD45-targeted immunocytokines have lower internalization rates relative to wild-type counterparts, leading to sustained downstream cis and trans signaling between lymphocytes. A single intratumoral dose of alphaCD45-interleukin (IL)-12 followed by a single dose of alphaCD45-IL-15 eradicated treated tumors and untreated distal lesions in multiple syngeneic mouse tumor models without toxicity. Mechanistically, CD45-targeted cytokines reprogrammed tumor-specific CD8(+) T cells in the tumor-draining lymph nodes to have an antiviral transcriptional signature. CD45 anchoring represents a broad platform for protein retention by host immune cells for use in immunotherapy. |
