William A. Nyberg
About me
T cells expressing chimeric antigen receptors (CAR) have transformed cell therapies against some hematological cancers. Genome engineering is a fast-moving field and recent advances in engineering of primary T cells have expanded the horizon of CAR-T cell therapies, and unlocked the potential to target a broader range of malignancies and to improve overall T cell fitness. However, the manufacturing process of CAR-T cell therapies is time-consuming, complex and costly. This limits the potential reach of CAR-T cell therapies around the world. The overall goal of our research is to develop strategies for precisely engineered CAR-T cell therapies in vivo, and to use the latest technologies in advanced gene engineering to improve their efficacy. To succeed with these goals, we will mainly use adeno-associated viruses (AAV) targeting T cells to generate gene targeted CAR-T cells in vivo. These AAVs are combined with a variety of in vivo delivery vehicles for Cas9 nucleases, such as viral-like particles (VLP) or lipid nanoparticles (LNP). These studies will be performed in translational humanized mouse models and in fully immunocompetent syngeneic mouse models. The second part of our mission is to improve CAR-T cell therapies by advances gene engineering, to succeed with this goal we are using pooled knock-in screens of large libraries of synthetic receptors that help CAR-T cells relay inhibitory signals commonly found in tumor microenvironments (TME) to co-stimulatory signals that may improve T cell fitness. These studies are performed in immunocompetent mouse models that represent a wide variety of different TME challenges. Our research promises to democratize access to advanced CAR-T cell therapies by avoiding ex vivo cell manufacturing, as well as improve the potential for CAR-T cell therapies in challenging solid tumors.
Articles
- Article: NUCLEIC ACIDS RESEARCH. 2025;53(6):gkaf213Pulgarin DV; Pelo N; Ferrandiz L; Trselic T; Nyberg WA; Bowlin G; Espinosa A
- Article: SCIENTIFIC REPORTS. 2025;15(1):5749Sytsma BJ; Allain V; Bourke S; Faizee F; Fathi M; Ferreira LMR; Brewer WJ; Li L; Pan FL; Rothrock AG; Nyberg WA; Li Z; Wilson LH; Berdeaux R; Eyquem J; Pawell RS
- Article: IMMUNITY. 2025;58(2):499-512.e7Nyberg WA; Wang CH; Ark J; Liu C; Clouden S; Qualls A; Caryotakis S; Wells E; Simon K; Garza C; Bernard P-L; Lopez-Ichikawa M; Li Z; Seo J; Kimmerly GR; Muldoon JJ; Chen PA; Li M; Liang H-E; Kersten K; Rosales A; Kuhn N; Ye CJ; Gardner JM; Molofsky A; Ricardo-Gonzalez RR; Asokan A; Eyquem J
- Article: NATURE BIOTECHNOLOGY. 2025;:1-11Chang CR; Vykunta VS; Lee JHJ; Li K; Kochendoerfer C; Muldoon JJ; Wang CH; Mazumder T; Sun Y; Goodman DB; Nyberg WA; Liu C; Allain V; Rothrock A; Ye CJ; Marson A; Shy BR; Eyquem J
- Journal article: BIORXIV. 2024;:2024.07.11.603114Kuhn NF; Zaleta-Linares I; Nyberg WA; Eyquem J; Krummel MF
- Journal article: BIORXIV. 2024;:2024.06.25.600671Sytsma BJ; Allain V; Bourke S; Faizee F; Fathi M; Berdeaux R; Ferreira LMR; Brewer WJ; Li L; Pan FL; Rothrock AG; Nyberg WA; Li Z; Wilson LH; Eyquem J; Pawell RS
- Journal article: BIORXIV. 2024;:2024.02.06.576175Chang CR; Vykunta VS; Goodman DB; Muldoon JJ; Nyberg WA; Liu C; Allain V; Rothrock A; Wang CH; Marson A; Shy BR; Eyquem J
- Article: CELL. 2023;186(19):4216-4234.e33Blaeschke F; Chen YY; Apathy R; Daniel B; Chen AY; Chen PA; Sandor K; Zhang W; Li Z; Mowery CT; Yamamoto TN; Nyberg WA; To A; Yu R; Bueno R; Kim MC; Schmidt R; Goodman DB; Feuchtinger T; Eyquem J; Jimmie C; Carnevale J; Satpathy AT; Shifrut E; Roth TL; Marson A
- Article: CELL. 2023;186(2):446-460.e19Nyberg WA; Ark J; To A; Clouden S; Reeder G; Muldoon JJ; Chung J-Y; Xie WH; Allain V; Steinhart Z; Chang C; Talbot A; Kim S; Rosales A; Havlik LP; Pimentel H; Asokan A; Eyquem J
- Article: EMBO REPORTS. 2023;24(1):e54944Nyberg WA; Velasquez-Pulgarin DA; He T; Sjostrand M; Pelle L; Covacu R; Espinosa A
- Article: NATURE. 2022;609(7925):174-182Carnevale J; Shifrut E; Kale N; Nyberg WA; Blaeschke F; Chen YY; Li Z; Bapat SP; Diolaiti ME; O'Leary P; Vedova S; Belk J; Daniel B; Roth TL; Bachl S; Anido AA; Prinzing B; Ibanez-Vega J; Lange S; Haydar D; Luetke-Eversloh M; Born-Bony M; Hegde B; Kogan S; Feuchtinger T; Okada H; Satpathy AT; Shannon K; Gottschalk S; Eyquem J; Krenciute G; Ashworth A; Marson A
- Article: ANNALS OF THE RHEUMATIC DISEASES. 2022;81(8):1151-1161Meisgen S; Hedlund M; Ambrosi A; Folkersen L; Ottosson V; Forsberg D; Thorlacius GE; Biavati L; Strandberg L; Mofors J; Ramskold D; Ruhrmann S; Meneghel L; Nyberg W; Espinosa A; Hamilton RM; Franco-Cereceda A; Hamsten A; Olsson T; Greene L; Eriksson P; Gemzell-Danielsson K; Salomonsson S; Kuchroo VK; Herlenius E; Kockum I; Sonesson S-E; Wahren-Herlenius M
- Article: IMMUNOLOGY. 2020;159(3):335-343Sjoestrand M; Carow B; Nyberg WA; Covacu R; Rottenberg ME; Espinosa A
- Article: EUROPEAN JOURNAL OF IMMUNOLOGY. 2019;49(2):313-322miR-31 regulates energy metabolism and is suppressed in Tcells from patients with Sjogren's syndromeJohansson A; Nyberg WA; Sjostrand M; Moruzzi N; Bergman P; Khademi M; Andersson M; Piehl F; Berggren P-O; Covacu R; Jagodic M; Espinosa A
- Article: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 2016;473(4):789-794Nyberg WA; Espinosa A
- Article: EXPERIMENTAL CELL RESEARCH. 2015;333(1):105-115Mertens-Walker I; Lisle JE; Nyberg WA; Stephens CR; Burke L; Rutkowski R; Herington AC; Stephenson S-A
All other publications
- Conference publication: EUROPEAN JOURNAL OF IMMUNOLOGY. 2024;54:158Pulgarin DV; Pelo N; Ferrandiz L; Trselic T; Nyberg W; Bowlin G; Espinosa A
- Preprint: BIORXIV. 2023;BIORXIVPulgarin DV; Pelo N; Ferrandiz L; Trselic T; Nyberg WA; Bowlin G; Espinosa A
- Preprint: BIORXIV. 2022Blaeschke F; Chen YY; Apathy R; Li Z; Mowery C; Nyberg W; To A; Yu R; Bueno R; Kim MC; Schmidt R; Goodman D; Feuchtinger T; Eyquem J; Ye CJ; Shifrut E; Roth T; Marson A
- Preprint: BIORXIV. 2019Nyberg W; He T; Sjöstrand M; Velasquez-Pulgarin D; Pellé L; Covacu R; Espinosa A
Grants
- Improving CAR-T cell therapies through AAV-mediated genetic engineeringEuropean Research Council1 January 2025 - 31 December 2029
- SciLifeLab FellowKarolinska Institutet1 July 2024 - 30 June 2030
- Generating CAR-T cells in vivo by gene targeting.Swedish Society for Medical Research1 June 2024 - 1 June 2028
- Swedish Research Council1 January 2024 - 31 December 2027T cells expressing chimeric antigen receptors (CAR) have transformed cell therapies against some cancers. As a postdoctoral fellow, I evolved a synthetic adeno-associated virus (AAV) with tropism against murine T cells, providing a unique tool to study gene targeted T cells in immunocompetent cancer models. In this proposal, capitalizing on my break-through, I will develop novel strategies to generate functional gene targeted CAR-T cells in vivo, optimizing AAV delivery in immunocompetent mouse models and combining these methods with cutting-edge technologies for Cas9-delivery for T cell-specific gene editing. Building a collaborative team in a strong translational research environment, we will evaluate the therapeutic potential of in vivo generated CAR-T cells against syngeneic tumors in immunocompetent mice, and include T cell adjuvant therapies to improve the efficacy. The ultimate goal of my proposal is to develop methods that can be translated to clinical trials in humans. Therefore, we will establish a humanized mouse model that allows for targeting of human T cells in vivo, in which key findings from this research project will be translated for proof-of-concept experiments. As the first ever study of gene targeted T cells in vivo, my research will provide in-depth profiling of in vivo engineered CAR-T cells and their therapeutic potential. This study is a necessary first step forwards toward accessible and affordable in vivo generated CAR-T cell therapies in humans.
Employments
- Assistant Professor, Department of Medicine, Huddinge, Karolinska Institutet, 2024-2030
Degrees and Education
- Degree Of Doctor Of Philosophy, Department of Medicine, Solna, Karolinska Institutet, 2019
- Degree Of Master Of Medical Science 120 Credits, Karolinska Institutet, 2014
- Degree Of Bachelor Of Medical Science, Karolinska Institutet, 2012