Viral based vaccine TG4010 induces broadening of specific immune response and improves outcome in advanced NSCLC

Tosch, Caroline; Bastien, Bérangère; Barraud, Luc; Grellier, Benoit; Nourtier, Virginie; Gantzer, Murielle; Limacher, Jean Marc; Quéméneur, Éric; Bendjama, Kaidre; Préville, Xavier

doi:10.1186/s40425-017-0274-x

Cited by 47 publications

(32 citation statements)

References 29 publications

(37 reference statements)

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“…In contrast, in lung cancer, a randomised study showed that the delivery of MUC1 in an MVA vaccine (TG4010) in the TIME study could lead to clinical benefit [ 163 ]. The study is further noteworthy as the authors showed convincingly that vaccination also induced T-cell reactivities against molecules that were not encoded in the vaccine [ 164 ]. This concept of ‘epitope spreading’ likely reflects the release of antigen from dying cancer cells, and if it can be reproduced in other trials, it would be an important feature of anti-cancer vaccination, both to be evaluated and as a path to broadening immune attack.…”

Section: Tumour-associated Antigens (Taas)mentioning

confidence: 99%

HNSCC: Tumour Antigens and Their Targeting by Immunotherapy

Witzleben

Wang

Laban

et al. 2020

Cells

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Head and neck squamous cell carcinomas (HNSCC) are a heterogeneous group of malignant tumours typically caused by alcohol and tobacco consumption, although an increasing number of HNSCC arise due to persistent infection with high-risk human papilloma virus (HPV). The treatment of HNSCC remains challenging, and the first-line setting is focused on surgery and chemoradiotherapy. A substantial proportion of HNSCC patients die from their disease, especially those with recurrent and metastatic disease. Among factors linked with good outcome, immune cell infiltration appears to have a major role. HPV-driven HNSCC are often T-cell rich, reflecting the presence of HPV antigens that are immunogenic. Tumour-associated antigens that are shared between patients or that are unique to an individual person may also induce varying degrees of immune response; studying these is important for the understanding of the interaction between the host immune system and the cancer. The resulting knowledge is critical for the design of better immunotherapies. Key questions are: Which antigens lead to an adaptive immune response in the tumour? Which of these are exploitable for immunotherapy? Here, we review the current thinking regarding tumour antigens in HNSCC and what has been learned from early phase clinical trials.

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Section: Tumour-associated Antigens (Taas)mentioning

confidence: 99%

HNSCC: Tumour Antigens and Their Targeting by Immunotherapy

Witzleben

Wang

Laban

et al. 2020

Cells

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“…MUC1-based clinical trials are currently ongoing, including retargeting human CD8 + and CD4 + T cells to tumor-associated MUC1 glycoforms ( 5 , 6 ). In addition, TG4010, a viral vaccine developed by Transgene SA, expresses full-length MUC1 and interleukin (IL)-2, and has demonstrated an association between overall survival and vaccine-induced T-cell responses ( 7 ). Lakshminarayanan et al ( 8 ) have also constructed a tumor vaccine by covalent attachment of a T-helper epitope and an aberrantly glycosylated MUC1 peptide, which induces immunoglobulin (Ig) G antibodies and cytotoxic T lymphocytes (CTLs) against MUC1.…”

Section: Introductionmentioning

confidence: 99%

Synthetic MUC1 breast cancer vaccine containing a Toll‑like receptor 7 agonist exerts antitumor effects

et al. 2020

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Adjuvant immunotherapy has recently emerged as a potential treatment strategy for breast cancer. The tumor-associated protein mucin 1 (MUC1) has received increasing attention due to its high expression in numerous types of common tumors, in which MUC1 acts as a cancer antigen. However, the simple mixed composition of an adjuvant and a peptide is not a sufficient rationale for a MUC1 peptide-based vaccine. The present study developed a novel Toll-like receptor 7 (TLR7) agonist-conjugated MUC1 peptide vaccine (T7-MUC1), which elicited an effective immune response and a robust antitumor effect in a mouse breast cancer model. In vitro , T7-MUC1 significantly increased the release of cytokines in mouse bone marrow dendritic cells and spleen lymphocytes, and induced the dendritic cell-cytokine-induced killer response against tumor cells with high MUC1 expression. In vivo , it was observed that the 4T1 tumor weights in mice immunized with the T7-MUC1 conjugate were reduced by ≥70% compared with those in the control group. Furthermore, the therapeutic responses in vivo were attributed to the increase in specific humoral and cellular immunity, including high antibody titers, antibody-dependent cell-mediated cytotoxicity and cytotoxic T-lymphocyte activity. The percentages of CD3 + /CD8 + T-cells were significantly higher in the T7-MUC1 treatment group compared with those in the control group. Therefore, the results of the present study suggested that the T7-MUC1 vaccine inhibited tumor growth in mice and thus may have potential as a therapeutic candidate in clinical trials for breast cancer immunotherapy.

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“…Response to the viral vaccine was predicted by levels of natural killer (NK) cells and TG4010 plus chemotherapy improved progression-free survival compared with chemotherapy and placebo. Further studies on the patients and tumours from this trial indicate that TG4104 induces a broadening of the T-cell response to other tumour-associated antigens and the diversity of the T-cell response relates to response to therapy [ 22 ].…”

Section: Phase I/ii Trials Reported In the Literaturementioning

confidence: 99%

Latest developments in MUC1 immunotherapy

Taylor‐Papadimitriou

Burchell

Graham

et al. 2018

Biochemical Society Transactions

105

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Currently, there is renewed interest in attempting to recruit the host immune system to eliminate cancers, and within this renewed activity, MUC1 continues to arouse interest. MUC1 has been considered a possible therapeutic target for the past 30 years as it is up-regulated, aberrantly glycosylated and its polarization is lost in many adenocarcinomas. Moreover, MUC1 is expressed by some haematopoietic cancers, including acute myeloid leukaemia and myeloma. Although multiple clinical trials have been initiated and immune responses have been documented, effective clinical benefit worthy of approval for general application has not as yet been achieved. However, this does not appear to have quelled the interest in MUC1 as a therapeutic target, as shown by the increase in the number of MUC1-based clinical trials initiated in 2017 ( Figure 1). As with all translational studies, incorporating new relevant research findings into therapeutic strategy is difficult. Decisions are made to commit to a specific strategy based on the information and data available when the trial is initiated. However, the time required for preclinical studies and early trials can render the founding concept not always appropriate for proceeding to a larger definitive trial. Here, we summarize the attempts made, to date, to bring MUC1 into the world of cancer immunotherapy and discuss how research findings regarding MUC1 structure and function together with expanded knowledge of its interactions with the tumour environment and immune effector cells could lead to improved therapeutic approaches. Figure 1.Number of MUC1-targeted trials initiated each year.

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Viral based vaccine TG4010 induces broadening of specific immune response and improves outcome in advanced NSCLC

Cited by 47 publications

References 29 publications

HNSCC: Tumour Antigens and Their Targeting by Immunotherapy

HNSCC: Tumour Antigens and Their Targeting by Immunotherapy

Synthetic MUC1 breast cancer vaccine containing a Toll‑like receptor 7 agonist exerts antitumor effects

Latest developments in MUC1 immunotherapy

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