• Vaccine Name: MVA-MUC1-IL2 Vaccine (TG4010)
• Target Pathogen: Cancer
• Target Disease: Cancer
• Vaccine Ontology ID: VO_0007428
• Type: Recombinant vector vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Host Species as Laboratory Animal Model: Human
• Antigen: Full-length MUC1
• MUC1 gene engineering:
  • Type: Recombinant protein preparation
  • Description: (Hillman et al., 2017)
  • Detailed Gene Information: Click Here.
• Preparation: TG4010 (Transgene, SA) is a suspension of MVA–MUC1–IL-2 vector particles consisting of a recombinant, attenuated, Modified Vaccinia Ankara (MVA) virus containing the coding sequence for human MUC1 and IL-2. The MVA–MUC1–IL-2 vector (MVATG9931) was generated by homologous recombination in a subclone of MVA named N33 using transfer plasmid pTG9931, which carried the genes for MUC1 and IL-2 and flanking sequences surrounding Deletion II of MVA. MVA–MUC1–IL-2 was produced on primary chicken embryo fibroblasts (Hillman et al., 2017).
• Immunization Route: subcutaneous injection
• Description: A recombinant attenuated replication-deficient Modified Vaccinia Ankara (MVA) vector encoding full-length human MUC1 and IL-2 as an intrinsic local adjuvant; the MVA backbone provides additional viral danger signals and immunostimulatory activity (Liu et al., 2004). Also known as Mesmulogene Ancovacivec (NCIT_C2241). In human dendritic cells transduced ex vivo, MVA-MUC1-IL2 expressed predominantly highly glycosylated MUC1 (HMFG-1 glycoform) with low-level tumor-associated underglycosylated forms (Trevor et al., 2001). Administered intramuscularly in Phase I and subcutaneously in later trials, typically at 10⁸ pfu weekly for 6 weeks then every 3 weeks. In preclinical RENCA-MUC1 murine RCC, vaccine-then-radiation (8 Gy) achieved 55–58% complete responders and 60% long-term survival versus neither modality alone, with confirmed specific tumor immunity by rechallenge, IFN-γ ELISpot, and abscopal effect (Hillman et al., 2017). Phase I (mixed solid tumors, n=13): 4/13 SD 6–9 months, 5/13 MUC1-specific T-cell responses induced post-vaccination; 10⁸ pfu established as recommended dose (Rochlitz et al., 2003). Phase II breast cancer: 0 PR, limited SD, program terminated (Liu et al., 2004). Phase II prostate cancer (PSA failure, n=40): 13/40 ≥2× PSA-DT improvement (p=0.0008); 10 patients PSA stabilization >8 months; treatment well tolerated (Dreicer et al., 2009). Phase II metastatic RCC (n=37): TG4010 monotherapy then TG4010 plus IFN-α2a/IL-2 upon progression; 18% SD >6 months monotherapy, 30% SD >6 months combination; median OS 19.3 months; MUC1-specific CD8+ responses associated with longer OS (P<0.05) (Oudard et al., 2011). Phase IIb NSCLC (n=148): 6-month PFS 43.2% vs 35.1%, ORR 41.9% vs 28.4%; TrPAL identified as predictive biomarker: normal-TrPAL patients showed greater benefit, high-TrPAL patients showed worse outcomes with TG4010 (Quoix et al., 2011). Phase 2b/3 TIME NSCLC (n=222): HR 0.74 (p=0.019), ORR 40% vs 29%; TrPAL ≤Q3 non-squamous subgroup HR 0.59 for both PFS and OS; trial advanced to Phase 3 (Quoix et al., 2016). Consistently well tolerated across studies; grade 1–2 injection-site reactions, fatigue, fever/flu-like symptoms, and mild constitutional adverse events predominated (Rochlitz et al., 2003; Dreicer et al., 2009; Oudard et al., 2011; Quoix et al., 2011).

Human Response

• Immune Response: The combination of 8 Gy radiation and the MVA-MUC1-IL2 vaccine significantly delayed tumor growth compared to either treatment alone.When the MVA-MUC1-IL-2 vaccine was given before radiotherapy (8 Gy), there was 55–58% complete response and 60% long-term survival in mice. This strategy resulted in greater immune cell infiltration and more effective tumor destruction than the radiation-first strategy. Conversely, the radiation-first sequence resulted in 24–30% complete response and 30% survival at 70 days. Histological analysis revealed that tumors treated with both radiation and vaccine showed extensive tumor necrosis, infiltration by macrophages (F4/80+), CD8+ cytotoxic T cells, and CD4+ helper T cells. IFN-γ secretion confirmed tumor-specific T-cell activation. An abscopal effect was observed: tumors on the opposite side of the treated area were also rejected, indicating a systemic immune response. Mice that responded to the combined therapy were immune to rechallenge with Renca-MUC1 cells, demonstrating that the treatment induced tumor-specific immunity (Hillman et al., 2017).