Transgene (Paris:TNG), a biotech company that designs and develops viral-based immunotherapies, recently published two papers supporting the efficacy and mechanism of action of its therapeutic vaccine TG4010 (Press release, Transgene, OCT 12, 2017, View Source [SID1234520883]). After successful completion of the phase 2b TIME trial for combination of TG4010 and chemotherapy (Quoix et al. Lancet Oncol., 2015), these two peer-reviewed articles support the ongoing development of the product in combination with immune checkpoint inhibitors (ICIs) in advanced NSCLC. More generally, they confirm the interest in viral vectors as immunotherapeutics.
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In this paper, based on samples from 78 patients of the TIME trial, Transgene provides the first data linking directly the development of a specific cellular immune response with an improved clinical benefit in patients with advanced NSCLC upon vaccination with a viral vector.
It was shown that the significantly longer overall survival (OS) of patients treated with TG4010 is correlated with the diversity and intensity of CD8+ T cell responses against the MUC1 antigen.
Treatment with TG4010 also led to a broadening of immune response to other tumor-associated antigens that were not targeted by the vaccine. This is the first report of such a mechanism of epitope spreading for a virus-based immunotherapeutic product. This spreading might contribute to the enrichment of the diversity of the anti-cancer response.
These results support the causality of T-cell response in improved survival in NSCLC, and strengthen the rationale for combination with ICIs to exploit the broad CD8+ T cell repertoire induced by TG4010 vaccination.
"Sequential administration of MVA-based vaccines and PD-1/PD-L1-blocking antibodies confers measurable benefits on tumor growth and survival: preclinical studies with MVA-βGal and MVA-MUC1 (TG4010) in a murine tumor model." By Remy-Ziller et al., Human Vaccines & Immunotherapeutics, 2017 Sep (19:0), doi: 10.1080/21645515.2017.1373921. epub ahead of print
Transgene further demonstrates the benefit of administration of MVA-vaccines, and ICIs in a preclinical metastatic model. Treatment with MVA vectors showed increased survival rates, and led to the accumulation of CD3dimCD8dim T cells in the lung and an upregulation of PD-1 was observed on these T cells.
Targeting the PD-1/PD-L1 pathway with ICIs in association with TG4010 treatment, at late stage of tumor development, enhanced the therapeutic activity induced by the vaccine, supporting the two ongoing clinical evaluation of TG4010 in combination with nivolumab.
About TG4010
TG4010 is an immunotherapy that has been designed to express the coding sequences of the MUC1 tumor-associated antigen and the cytokine, Interleukin-2 (IL2) in a modified vaccinia virus (MVA).
The combination of TG4010 immunotherapy and chemotherapy has demonstrated significant efficacy in terms of progression-free survival and overall survival in patients with advanced stage NSCLC (Quoix et al. Lancet Oncol. 2015). TG4010 is currently being investigated in combination with nivolumab (ICI) for the 2nd-line treatment of advanced NSCLC (NCT02823990). A trial in 1st-line treatment of NSCLC is expected to begin at the end of 2017, evaluating the combination regimen of TG4010 + nivolumab + chemotherapy in patients whose tumors express low or undetectable levels of PD-L1.