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Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Latest developments in MUC1 immunotherapy
Joyce Taylor-Papadimitriou1, Joy M Burchell2, Rosalind Graham2
1Breast Cancer Biology Lab, School of Cancer and Pharmaceutical Sciences, King's College London, London, U.K. joyce.taylor-papadimitriou@kcl.ac.uk.
Abstract:
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. ppbiost;46/3/659/BST20170400CF1F1BST-2017-0400CF1Figure 1.Number of MUC1-targeted trials initiated each year.
Insights
Despite decades of research and numerous clinical trials, MUC1 remains a promising cancer immunotherapy target. Further understanding of MUC1
Area of Science:
- Cancer immunotherapy
- Tumor immunology
- Molecular oncology
Background:
- MUC1 is a transmembrane protein overexpressed and aberrantly glycosylated in many adenocarcinomas and some hematological malignancies.
- MUC1 has been a target for cancer immunotherapy for over 30 years due to its altered expression and localization in cancer cells.
- Despite numerous clinical trials, significant clinical benefit from MUC1-targeted therapies has not yet been achieved.
Purpose of the Study:
- To review past and present efforts in developing MUC1-based cancer immunotherapies.
- To discuss how new insights into MUC1 structure, function, and tumor microenvironment interactions can improve therapeutic strategies.
Main Methods:
- Review of existing literature and clinical trial data on MUC1-targeted cancer immunotherapy.
- Analysis of MUC1's role in cancer progression and immune evasion.
- Discussion of emerging research on MUC1 structure, function, and interactions within the tumor microenvironment.
Main Results:
- MUC1 remains a compelling target for cancer immunotherapy, with sustained interest and increasing clinical trials.
- Challenges in translating preclinical findings to clinical success have hindered widespread application.
- Recent research provides a deeper understanding of MUC1's complex role in cancer and immunity.
Conclusions:
- Continued research into MUC1's biology is crucial for overcoming current therapeutic limitations.
- Integrating new knowledge of MUC1 structure, function, and its interactions with the immune system can lead to more effective cancer immunotherapy strategies.
- The potential of MUC1 as a therapeutic target warrants further investigation and innovative approaches.
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