ArticleCancer immunology research2023
mWTX-330, an IL-12 INDUKINE Molecule, Activates and Reshapes Tumor-Infiltrating CD8+ T and NK Cells to Generate Antitumor Immunity.
Article in Cancer immunology research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 17 citations in OpenAlex.
- Article
- Cytokine fusion proteins for solid tumor therapy: mechanistic insights and clinical advances.Journal of hematology & oncology · 2026Review
- αHSA-proIL-12: A Tumor-Conditional IL-12 Prodrug with Reduced Systemic Toxicity and Potent Antitumor Activity.International journal of molecular sciences · 2026Article
- Co-stimulatory signal deficiency impairs cytotoxic T lymphocyte function in tumor immune evasion: molecular mechanisms and therapeutic implications.Journal of translational medicine · 2026Review
- A modular platform for Sterically Masked Activated Cytokines (SMACks).Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- IL-12-secreting CAR-T cells reprogram the tumor microenvironment and improve efficacy against heterogeneous models of glioblastoma.Journal for immunotherapy of cancer · 2026Article
- Skeletal muscle dysfunction induced by cancer immunotherapy: mechanistics insights and surgical implications.Frontiers in immunology · 2026Review
- Protein engineering to overcome limitations of key cytokines in cancer immunotherapy: current approaches and future perspectives.Immuno-oncology technology · 2025Review
- Identifying protease-activated targets and exploring therapeutic applications.Expert opinion on therapeutic targets · 2025Review
- Click-to-Release for Controlled Immune Cell Activation: Tumor-Targeted Unmasking of an IL12 Prodrug.Pharmaceuticals (Basel, Switzerland) · 2025Article
- FcRn-silencing of IL-12Fc prevents toxicity of local IL-12 therapy and prolongs survival in experimental glioblastoma.Nature communications · 2025Article
- Nanobody-Targeted Conditional Antimicrobial Therapeutics.ACS nano · 2025Article
- Uncovering the interleukin-12 pharmacokinetic desensitization mechanism and its consequences with mathematical modeling.CPT: pharmacometrics & systems pharmacology · 2025Article
- Expression of Interleukin-8, Interleukin-12 and Interleukin-13 in Esophageal Squamous Cell Carcinoma: Biomarker Potentiality and Prognostic Significance.Journal of gastrointestinal cancer · 2024Article
- CLN-617 Retains IL2 and IL12 in Injected Tumors to Drive Robust and Systemic Immune-Mediated Antitumor Activity.Cancer immunology research · 2024Article
- XTX301, a Tumor-Activated Interleukin-12 Has the Potential to Widen the Therapeutic Index of IL12 Treatment for Solid Tumors as Evidenced by Preclinical Studies.Molecular cancer therapeutics · 2024Article
- Strategies to therapeutically modulate cytokine action.Nature reviews. Drug discovery · 2023Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IL-12 is a pleotropic inflammatory cytokine, which has broad stimulatory effects on various immune cell populations, making it an attractive target for cancer immunotherapy. However, despite generating robust antitumor activity in syngeneic murine tumor models, clinical administration of IL-12 has been limited by severe toxicity. mWTX-330 is a selectively inducible INDUKINE molecule comprised of a half-life extension domain and an inactivation domain linked to chimeric IL-12 by tumor protease-sensitive linkers. Systemic administration of mWTX-330 in mice was well tolerated, resulted in robust antitumor immunity in multiple tumor models, and preferentially activated tumor-infiltrating immune cells rather than immune cells present in peripheral tissues. Antitumor activity was dependent on in vivo processing of the protease cleavable linkers and required CD8+ T cells for full efficacy. Within the tumor, mWTX-330 increased the frequency of cross-presenting dendritic cells (DC), activated natural killer (NK) cells, skewed conventional CD4+ T cells toward a T helper 1 (TH1) phenotype, drove regulatory T cells (Treg) fragility, and increased the frequency of polyfunctional CD8+ T cells. mWTX-330 treatment also increased the clonality of tumor-infiltrating T cells by expanding underrepresented T-cell receptor (TCR) clones, drove CD8+ T and NK cells towards increased mitochondrial respiration and fitness, and decreased the frequency of TOX+ exhausted CD8+ T cells within the tumor. A fully human version of this INDUKINE molecule was stable in human serum, was reliably and selectively processed by human tumor samples, and is currently in clinical development.
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