ArticleFrontiers in immunology2024
Self-delivering RNAi immunotherapeutic PH-762 silences PD-1 to generate local and abscopal antitumor efficacy.
Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06014086 (Dose Escalation Study of Neoadjuvant Intratumoral PH-762 for Cutaneous Squamous Cell Carcinoma, Melanoma, or Merkel Cell Carcinoma), which is not on this map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Dose Escalation Study of Neoadjuvant Intratumoral PH-762 for Cutaneous Squamous Cell Carcinoma, Melanoma, or Merkel Cell Carcinoma
Who cites it
4 citing papers in PubMed.
- Targeting Immune Checkpoint Proteins in Cancer Therapy and the Potential of RNAi-Based Immunotherapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities.Biomolecules · 2026Review
- Exploring the Potential of Receptor Silencing in the Tumor Microenvironment by RNA Interference.Biomolecules · 2026Review
- Emerging roles of tsRNAs in programmed cell death and disease therapeutics: challenges, opportunities, and future directions.Non-coding RNA research · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objective: Immunotherapeutic inhibition of PD-1 by systemically administered monoclonal antibodies is widely used in cancer treatment, but it may cause severe immune-related adverse events (irSAEs). Neoadjuvant PD-1 inhibition before surgery has shown promise in reducing recurrence by stimulating durable antitumor immunity. Local intratumoral (IT) immunotherapy is a potential strategy to minimize irSAEs, but antibodies have limited tumor penetration, making them less suitable for this approach. Therapeutic self-delivering RNAi (INTASYL) is an emerging modality well-suited for neoadjuvant immunotherapy. This study presents preclinical proof-of-concept for PH-762, an INTASYL designed to silence PD-1, currently in clinical development for advanced cutaneous malignancies (ClinicalTrials.gov#NCT06014086). Methods and analysis: PH-762 pharmacology was characterized Results: PH-762 was rapidly internalized by human T cells, silencing PD-1 mRNA and decreasing PD-1 surface protein, enhancing TCR-stimulated IFN-γ and CXCL10 secretion. Conclusion: These data support PH-762 as a promising candidate for neoadjuvant immunotherapy in clinical studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.