News Watch: EV × Neurons × Tumor Immunity—Tumor-derived sEVs reprogram nociceptors to drive immunosuppression (with a look at IL-6/IL-6R blockade and potential label expansion) Vol.2

Appendix: IL-6R Inhibitors & Company Landscape (as of Aug 2025)

A quick map of who owns which IL-6R blockers and current approved uses, to inform combo trials and partnering around the neuro-immune loop discussed above.

Approved agents (receptor blockade: anti-IL-6R)

• Tocilizumab (Actemra/RoActemra)
  Owner: Roche (Genentech in US; Chugai in JP and other regions)
  Indications: RA, GCA, JIA (PJIA/SJIA), CAR-T–induced CRS, selected regions also SSc-ILD/COVID-19; IV and SC forms. See latest US label (2025) and Genentech HCP info. FDA Access DataGene.comactemra
• Sarilumab (Kevzara)
  Owners: Sanofi & Regeneron (co-development)
  Indications: RA, polymyalgia rheumatica (PMR) (US FDA approval in 2023); SC formulation. FDA Access DataRegeneron InvestorsDrugs.com
• Satralizumab (Enspryng)
  Owner: Roche (Genentech/Chugai)
  Indication: NMOSD (AQP4+); monthly SC dosing enabled by recycling-antibody tech. FDA Access DataGene.comRoche
• Levilimab (ILSIRA) (regional approval)
  Owner: BIOCAD (Russia)
  Indications/Status: fast-track approval in Russia for COVID-19–related complications; RA development noted; limited global reach to date. eng.biocad.ruantibodysociety.org

Biosimilars to tocilizumab

• TOFIDENCE™ (tocilizumab-bavi) — Biogen/Samsung Bioepis; US FDA approved 2023. investors.biogen.com
• Avtozma® (CT-P47) — Celltrion; US FDA approved Jan 2025 (rheumatologic indications). Center for Biosimilars
  (Other regions have additional tocilizumab biosimilar activity; always check local labels.) Pearce IP

Pipeline (receptor blockade: for reference)

• Vobarilizumab (ALX-0061) — originated at Ablynx (now Sanofi); anti-IL-6R Nanobody; mixed P2 outcomes (e.g., SLE). Oncology repurposing unknown. FirstWord PharmaLarvol Delta

Note: While we focus on IL-6R, ligand blockers (anti-IL-6)—e.g., siltuximab (Janssen; MCD), clazakizumab (CSL Vifor; transplant rejection), ziltivekimab (Novo; CV/CKD)—could be compared mechanistically for MDSC attenuation vs. T-cell exhaustion relief in oncology combos.

My Perspective (Partnering & Deployment)

• Ready-to-test combos are most practical with Actemra (Roche/Chugai) and Kevzara (Sanofi/Regeneron) thanks to supply scale, SC/IV options, and established safety. Enspryng’s long-interval SC paradigm informs intermittent or induction-limited strategies. FDA Access Data+2FDA Access Data+2
• Biosimilars (Biogen/Samsung Bioepis; Celltrion) may improve affordability and access, critical for biomarker-selected prospective trials. investors.biogen.comCenter for Biosimilars
• Trial sketch: In HNSCC/melanoma with high-pain/high-IL-6/high-MDSC signatures, compare ICI ± IL-6R blockade, with pain/QOL co-primary endpoints, and timed/short-course dosing to avoid over-immunosuppression.

References (Key)

• Restaino AC, et al. Sci Signal. 2025. Tumor-infiltrating nociceptor neurons promote immunosuppression.
• Boyd L, et al. Sci Signal. 2025. Tumor-derived sEVs reprogram sensory nerves… (Focus)
• Inyang KE, et al. PAIN. 2023/2024. HPV+ HNSCC-derived sEVs communicate with TRPV1+ neurons to mediate cancer pain.
• Mancusi R, et al. Nature. 2023. The neuroscience of cancer.
• Tsukamoto H, et al. Cancer Res. 2018. Combined blockade of IL-6 and PD-1/PD-L1.
• Hailemichael Y, et al. Nat Cancer. 2022. IL-6 blockade + ICB: maintains antitumor immunity while mitigating autoimmunity.
• EULAR Consensus (Aletaha D, 2023). Blocking IL-6R: indications incl. RA/GCA/JIA/NMOSD.
• Clinical evidence/registries: COLAR and early ICI+TCZ studies.

世界最先端の治療薬を創る〜製薬会…

News Watch: EV × Neurons × Tumor Immunity—Tumor-derived sEVs reprogram nociceptors to drive immunosu… Fresh data in Science Signaling (2025) show that tumor-derived small extracellular vesicles (sEVs) reprogram TRPV1+ nociceptors, boosting IL-6 and Substance

This blog was edited by Morningglorysciences team.