Our overall goal is to develop novel targeted immunotherapies for patients with hematologic malignancies. The group develops adoptive T cell therapies with native or engineered receptors and evaluates combinatorial strategies. The objective is to efficiently target tumor cells, mitigate immunosuppressive tumor microenvironment factors, favor tumor-targeted migration and longevity of transferred T cells, control potential toxicities, identify novel personalized targets, and move developments to the clinic.
- To redirect human T specificity to target hematologic malignancies by genetic engineering (chimeric antigen receptors, transgenic T cell receptors, others)
- To develop combinatorial approaches to engineered T cell therapy targeting both the tumor cells and their microenvironment (e.g. engineer tumor-directed migration, resistance to immune inhibitory signals)
- To engineer signaling switches in T cells that revert tumor-associated immune inhibitory signals.
- To assess tumor microenvironment modulation upon adoptive transfer of engineered T cells, including omics and spatial technologies
- To evaluate 3D culture systems to better model the tumor microenvironment in vitro and use them to evaluate transgenic T cell function
- To identify immunogenic tumor neo-antigens in patients with hematologic malignancies and to isolate their neo-antigen specific TCRs for personalized medicine applications.
- We apply principles from immunology, hematology, cancer and systems biology, use gene transfer and editing technologies to engineer T cells, and collaborate with experts in protein engineering, gene editing, proteomics/ peptidomics, immunomonitoring, bioinformatics, bioengineering, clinical hematology and immuno-oncology.
- Camviel N, Wolf B, Croce G, Gfeller D, Zoete V, Arber C. Both APRIL and antibody-fragment-based CAR T cells for myeloma induce BCMA downmodulation by trogocytosis and internalization. J Immunother Cancer. (2022).
- Omer B, Cardenas MG, Pfeiffer T,... Arber C, Rooney CM. A Costimulatory CAR Improves TCR-based Cancer Immunotherapy. Cancer Immunol Res. (2022).
- Rath JA*, Bajwa G*, Carreres B, Hoyer E, Gruber I, Martínez-Paniagua MA, Yu Y, Nouraee N, Sadeghi F, Wu M, Wang T, Hebeisen M, Rufer N, Varadarajan N, Ho PC, Brenner MK, Gfeller D, Arber C. Single-cell transcriptomics identifies multiple pathways underlying potent anti-tumor function of TCR and CD8ab engineered human CD4+ T cells. Science Advances. (2020).
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