Bruno Silva-Santos

Bruno Miguel de Carvalho Silva-Santos
Instituto de Medicina Molecular (iMM), Lisbon
Project Leader

Next-generation CAR-DOT cells for allogeneic adoptive cancer immunotherapy.

• Pablo Menéndez Bujan
  Institut de Recerca contra la Leucèmia Josep Carreras (IJC), Barcelona

Our project aimed to generate a new chimeric antigen receptor (CAR)-T cell product suitable for allogeneic immunotherapy of cancer, based on Human Leukocyte Antigen (HLA)-independent Delta One T (DOT) cells. We have engineered DOT cells with a CAR specific for the myeloid cell antigen, CD123, in order to target acute myeloid leukemia (AML). We have characterized and established the proof-of-concept for CD123CAR-DOT cells in various pre-clinical models of AML. We showed that these cells were much more efficient in targeting CD123+ AML cell lines or patient samples in vitro than mock-transduced DOT cells. Using a transplantable patient-derived xenograft model we also showed that CD123CAR-DOT cells are very efficient in controlling AML growth in vivo, even upon tumor re-challenge. Taken together, we were able to generate a new platform for allogeneic use of CAR-T cells, with very promising pre-clinical anti-tumor activity against the deadliest hematological malignancy, AML.

Group Leader of the Immuno-Oncology Lab at iMM for 18 years, Dr. Silva-Santos is also the Vice-Director of the IMM and Full Professor at the Faculty of Medicine of the University of Lisbon.

He is an international leader in Tumour Immunology, with a focus on gamma-delta T cells. He co-founded Lymphact, an iMM spin-off company that started in 2013 and was acquired by GammaDelta Therapeutics (London, UK) in 2018, and later (2022) incorporated in Takeda Pharmaceutical Co (Boston, USA).

Bruno Silva-Santos developed his PhD work at The London Research Institute and his post-doctoral work at King’s College London. He has published over 100 peer-reviewed papers in multiple prestigious journals, and he has been distinguished with nominations, awards and grants, from the European Molecular Biology Organization (EMBO), the European Research Council (ERC), the International Cytokine Society (ICS) and the European Academy of Tumour Immunology (EATI). He was elected EMBO Member in 2019. (Read full CV).

We are interested in the differentiation of T lymphocytes and their roles in cancer immunity. We have a special focus on unconventional gamma-delta (γδ) T cells, which we study from their development in the thymus to their effector functions in the tumor microenvironment. We employ pre-clinical models with murine and human cells to identify new molecular mechanisms involved in γδ T cell differentiation and responses, namely to tumor challenge. Our ultimate goal is to develop novel γδ T cell-based immunotherapies for cancer.

Instituto de Medicina Molecular João Lobo Antunes (iMM)
Edifício Egas Moniz
Avenida Professor Egas Moniz
1649-028 Lisboa, Portugal
Tel.: (+351) 217 999 411 Ext.: 47238

Email: [email protected]
Twitter: @BSilva_Santos