Dr Francis Mussai is a Clinical Senior Lecturer with a strong research interest in exploring the immunosuppressive microenvironment generated by paediatric malignancies.
Clinical Senior Lecturer, Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham.
Background and Research focus
Dr Francis Mussai is a Clinical Senior Lecturer in Paediatric Oncology in the Institute of Immunology and Immunotherapy. His research is focused on understanding the interaction between adult and paediatric cancers and the immune system. In particular his group is interested in how cancers alter metabolism or induce immunosuppressive myeloid cells such as myeloid-derived suppressor cells (MDSCs), to escape from being targeted and killed by patients’ immune cells. Working in conjunction with Dr Carmen De Santo, the group is developing a number of therapeutic approaches ranging from novel drugs to reactivate the immune microenvironment, development of Chimeric-Antigen Receptor T cells (CAR-T) or target cancer metabolism. Clinical trials based on the group’s research are currently underway.
Paediatric oncology; neuroblastoma; leukaemia; myeloid derived suppressor cells; immunosuppressive environment, arginine metabolism, CAR-T cells, immunotherapy.
Dr Mussai’s research has been funded by Cancer Research UK, the Medical Research Council, the Amber Phillpott Trust, Birmingham Children’s Hospital Research Fund, Children with Cancer, the Stiliyan Petrov Foundation, Niayah’s Fund, Neuroblastoma UK, and generous donation by Friends and Alumni of the University.
In addition to his research commitments, Francis is an honorary Paediatric Oncology Consultant at the Birmingham Children’s Hospital. Working with colleagues in the UK and Europe he continues to work on early phase clinical trials of novel therapeutic drugs for paediatric cancers, as well as undertake out-patient clinics and ward rounds of in-patients. He has established a leading international Fellowship programme for doctors from around the world to undergo training in Heamatology-Oncology-Stem Cell Transplant at BCH.
De Santo C, Cheng P, Beggs A, Egan S, Bessudo A, Mussai F. Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma. J Hematol Oncol. 2018 May 18;11(1):68. doi:10.1186/s13045-018-0612-6.
Khanna S, Graef S, Mussai F, Thomas A, Wali N, Yenidunya BG, Yuan C, Morrow B, Zhang J, Korangy F, Greten TF, Steinberg SM, Stetler-Stevenson M, Middleton G, De Santo C, Hassan R. Tumor-Derived GM-CSF Promotes Granulocyte Immunosuppression in Mesothelioma Patients. Clin Cancer Res. 2018 Jun 15;24(12):2859-2872. doi:10.1158/1078-0432.CCR-17-3757
De Santo C, Booth S, Vardon A, Cousins A, Tubb V, Perry T, Noyvert B, Beggs A, Ng M, Halsey C, Kearns P, Cheng P, Mussai F. The arginine metabolome in acute lymphoblastic leukemia can be targeted by the pegylated-recombinant arginase I BCT-100. Int J Cancer. 2018 Apr 1;142(7):1490-1502. doi: 10.1002/ijc.31170. Epub 2017 Dec 26.
Fultang L, Vardon A, De Santo C, Mussai F. Molecular basis and current strategies of therapeutic arginine depletion for cancer. Int J Cancer. 2016 Aug 1;139(3):501-9. doi: 10.1002/ijc.30051. Epub 2016 Apr 15. Review
Mussai F, Egan S, Hunter S, Webber H, Fisher J, Wheat R, McConville C, Sbirkov Y, Wheeler K, Bendle G, Petrie K, Anderson J, Chesler L, De Santo C. Neuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity. Cancer Res. 2015 Aug1;75(15):3043-53. doi: 10.1158/0008-5472.CAN-14-3443. Epub 2015 Jun 8.
Mussai F, Egan S, Higginbotham-Jones J, Perry T, Beggs A, Odintsova E, Loke J, Pratt G, U KP, Lo A, Ng M, Kearns P, Cheng P, De Santo C. Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target. Blood.2015 Apr 9;125(15):2386-96. doi: 10.1182/blood-2014-09-600643. Epub 2015 Feb 20.
Mussai FJ, Yap C, Mitchell C, Kearns P. Challenges of clinical trial design for targeted agents against pediatric leukemias. Front Oncol. 2015 Jan 6;4:374.doi: 10.3389/fonc.2014.00374. eCollection 2014. Review.
Mussai FJ, De Santo C, Abu-Dayyeh I, Booth S, Quek L, McEwen-Smith R Qureshi A, Dazzi F, Vyas P, Cerundolo V. 2013. Acute myeloid leukaemia creates an arginase-dependent immunosuppressive microenvironment. Blood; 122(5):749-58
Mussai F, De Santo C, Cerundolo V. (2012), Interaction between invariant NKT cells and Myeloid Derived Suppressor Cells in cancer patients: evidence and therapeutic opportunities. Journal of Immunotherapy, 35: 449-59
Mussai F, Campana D, Bhojwani D, Stetler-Stevenson M, Steinberg SM, Wayne AS, Pastan I. (2010) Cytotoxicity of the anti-CD22 immunotoxin HA22 (CAT-8015) against paediatric acute lymphoblastic leukaemia. British Journal of Haematology, 150: 352-358