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{{Authority control}}
[[Category:Cancer researchers]]
[[Category:Cancer researchers]]
[[Category:Immunotherapy]]
[[Category:Immunotherapy]]

Revision as of 14:54, 20 September 2023

Marcin Kortylewski
Born
Poznań, Poland
Years active1996-present
Academic background
Alma materAdam Mickiewicz University
Academic work
InstitutionsPoznań University of Medical Sciences

RWTH Aachen University H. Lee Moffitt Cancer Center & Research Institute

City of Hope National Medical Center
Websitehttps://www.linkedin.com/in/marcin-kortylewski-6841b220/

Marcin Kortylewski is a Polish American cancer researcher and immunologist. He is currently professor of immuno-oncology at the Beckman Research Institute of the City of Hope National Medical Center in Duarte, California.[1][2][3] His research has shown that the STAT3 protein plays a role in protecting cancers from immune responses and contributes to resistance to therapies.[4][5][6]. Later he developed a two-pronged strategy for cancer immunotherapy using simultaneous STAT3 inhibition and TLR9 immune stimulation.[7][8][9][10] Kortylewski invented platform strategy for delivery of oligonucleotides[11], such as siRNA[12][13][14], miRNA[15][16], decoy DNA[10][17] , antisense molecules[18][19] and others to selected immune cells.

Education

Kortylewski was born in Poznań, Poland. He received his M.S. in biotechnology from Adam Mickiewicz University and his Ph.D. in molecular biology from the Poznań University of Medical Sciences in Poznań, Poland. Dr. Kortylewski completed postdoctoral training in cancer biology in Institute of Biochemistry at RWTH Aachen in Germany and later in tumor immunology at H. Lee Moffitt Cancer Center in Tampa, Florida in USA.

Career

Kortylewski began his post-graduate career in 1999 as a postdoctoral fellow in Iris Behrman’s lab in RWTH Aachen/Institute of Biochemistry chaired by Peter C. Heinrich. During his tenure there, he co-authored numerous research articles[20]. Later, he moved to H. Lee Moffitt Cancer Center in Tampa, Florida in USA to train with Richard Jove and Hua Yu. In 2005, he became Assistant Research Professor in the Beckman Research Institute of the City of Hope National Medical Center in Duarte, California. There, he became tenured faculty in 2010 and full professor at the Department of Immuno-Oncology in 2021.

Kortylewski's research group focuses on understanding the mechanisms by which cancers evade the immune system and explores methods to enhance antitumor immune responses using DNA and RNA-based drugs.[1][2][3] In early 2000s, he demonstrated that tumors turn off immune cell activity using a transcription factor, STAT3.[6][21][22][23] His studies characterized STAT3 as a multitasking protein which prevents immune activation, while stimulating tumor vascularization and metastasis.[9][24][25] Kortylewski invented a two-pronged strategy for cancer immunotherapy combining STAT3 blocking using siRNA with triggering of immune receptor, Toll-like receptor 9 (TLR9) using CpG motif DNA.[26][12][27][14][28] Later on, he adopted the strategy as a platform for delivery of various oligonucleotide drugs to target oncogenic or immune regulators, such as STAT3[29][30], NF-kB or selected miRNAs[31][16][19] in human or mouse immune cells in vivo.

Kortylewski is a co-founder of a biomedical startup company, currently under the name Duet Biotherapeutics Inc., focused on advancing CpG-STAT3 inhibitors to clinical trials for cancer immunotherapy. [32][33] He is an active contributor to the field of immune-oncology and oligonucleotide therapeutics, serving on scientific and editorial boards of journals and various organizations.[34][35][36][37][38]

Awards

In 2016, Kortylewski was a recipient of an Outstanding Young Investigator Award from American Society of Gene and Cell Therapy, granted based on the contributions to the field of gene and cell therapy[39]. He received the award specifically for his work on “Eliminating Tumor Immune Defenses using Oligonucleotide Therapeutics”.

Patents

Patent Number Patent Name
US 9,688,982

US 10,253,318

Methods and compositions for the treatment of cancer or other diseases
US 9,976,147

US 10,829,765

STAT3 inhibitors and uses thereof
US 10,758,624 Compounds and compositions including phosphorothioated oligodeoxynucleotide, and methods of use thereof
US 10,711,272

US 11,186,840

CTLA-4 aptamer siRNA species

CTLA-4 Aptamer Conjugates

US 10,801,026 Compounds and compositions including phosphorothioated oligodeoxynucleotide, and methods of use thereof

References

  1. ^ a b "Marcin Kortylewski, Ph.D." City of Hope. 2022-05-11. Retrieved 2023-09-04.
  2. ^ a b Kortylewski, Marcin. "Marcin Kortylewski". ResearchGate.{{cite web}}: CS1 maint: url-status (link)
  3. ^ a b "Marcin Kortylewski". scholar.google.com. Retrieved 2023-09-04.
  4. ^ Yu, Hua; Kortylewski, Marcin; Pardoll, Drew (2007-01-01). "Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment". Nature Reviews Immunology. 7 (1): 41–51. doi:10.1038/nri1995. ISSN 1474-1733.
  5. ^ Minton, Kirsty. "Multi-tasking by STAT3". Nature Reviews Immunology. 9 (3): 149–149. doi:10.1038/nri2517. ISSN 1474-1741.
  6. ^ a b Stewart, C. Andrew; Trinchieri, Giorgio. "Reinforcing Suppression Using Regulators: A New Link between STAT3, IL-23, and Tregs in Tumor Immunosuppression". Cancer Cell. 15 (2): 81–83. doi:10.1016/j.ccr.2009.01.008.
  7. ^ Gantier, Michael P; Williams, Bryan R G. "siRNA delivery not Toll-free". Nature Biotechnology. 27 (10): 911–912. doi:10.1038/nbt1009-911. ISSN 1087-0156.
  8. ^ Kortylewski, Marcin; Swiderski, Piotr; Herrmann, Andreas; Wang, Lin; Kowolik, Claudia; Kujawski, Maciej; Lee, Heehyoung; Scuto, Anna; Liu, Yong; Yang, Chunmei; Deng, Jiehui; Soifer, Harris S; Raubitschek, Andrew; Forman, Stephen; Rossi, John J. "In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses". Nature Biotechnology. 27 (10): 925–932. doi:10.1038/nbt.1564. ISSN 1087-0156.
  9. ^ a b "STAT3: the "Achilles" heel for AML?". ashpublications.org. Retrieved 2023-09-04.
  10. ^ a b "A STAT3 decoy lures AML out of hiding". ashpublications.org. Retrieved 2023-09-04.
  11. ^ Kortylewski, Marcin; Moreira, Dayson. "Myeloid cells as a target for oligonucleotide therapeutics: turning obstacles into opportunities". Cancer Immunology, Immunotherapy. 66 (8): 979–988. doi:10.1007/s00262-017-1966-2. ISSN 0340-7004.
  12. ^ a b Nechaev, Sergey; Gao, Chan; Moreira, Dayson; Swiderski, Piotr; Jozwiak, Agnieszka; Kowolik, Claudia M.; Zhou, Jiehua; Armstrong, Brian; Raubitschek, Andrew; Rossi, John J.; Kortylewski, Marcin. "Intracellular processing of immunostimulatory CpG–siRNA: Toll-like receptor 9 facilitates siRNA dicing and endosomal escape". Journal of Controlled Release. 170 (3): 307–315. doi:10.1016/j.jconrel.2013.06.007. PMC 3742675. PMID 23777886.
  13. ^ Zhang, Qifang; Hossain, Dewan Md Sakib; Nechaev, Sergey; Kozlowska, Anna; Zhang, Wang; Liu, Yong; Kowolik, Claudia M.; Swiderski, Piotr; Rossi, John J.; Forman, Stephen; Pal, Sumanta; Bhatia, Ravi; Raubitschek, Andrew; Yu, Hua; Kortylewski, Marcin (2013-02-21). "TLR9-mediated siRNA delivery for targeting of normal and malignant human hematopoietic cells in vivo". Blood. 121 (8): 1304–1315. doi:10.1182/blood-2012-07-442590. ISSN 0006-4971.
  14. ^ a b Flemming, Alexandra. "CpG–siRNA deals double blow to tumours". Nature Reviews Immunology. 9 (11): 753–753. doi:10.1038/nri2665. ISSN 1474-1733.
  15. ^ "MicroRNA immunomodulating therapeutics". ashpublications.org. Retrieved 2023-09-11.
  16. ^ a b Su, Yu-Lin; Wang, Xiuli; Mann, Mati; Adamus, Tomasz P.; Wang, Dongfang; Moreira, Dayson F.; Zhang, Zhuoran; Ouyang, Ching; He, Xin; Zhang, Bin; Swiderski, Piotr M.; Forman, Stephen J.; Baltimore, David; Li, Ling; Marcucci, Guido (2020-01-16). "Myeloid cell–targeted miR-146a mimic inhibits NF-κB–driven inflammation and leukemia progression in vivo". Blood. 135 (3): 167–180. doi:10.1182/blood.2019002045. ISSN 0006-4971.
  17. ^ Soldevilla, Mario M.; Pastor, Fernando. "Decoy-Based, Targeted Inhibition of STAT3: A New Step forward for B Cell Lymphoma Immunotherapy". Molecular Therapy. 26 (3): 675–677. doi:10.1016/j.ymthe.2018.02.006. ISSN 1525-0016.
  18. ^ "STAT3 Inhibition Combined with CpG Immunostimulation Activates Antitumor Immunity to Eradicate Genetically Distinct Castration-Resistant Prostate Cancers". aacrjournals.org. Retrieved 2023-09-11.
  19. ^ a b Zhang, Bin; Nguyen, Le Xuan Truong; Li, Ling; Zhao, Dandan; Kumar, Bijender; Wu, Herman; Lin, Allen; Pellicano, Francesca; Hopcroft, Lisa; Su, Yu-Lin; Copland, Mhairi; Holyoake, Tessa L; Kuo, Calvin J; Bhatia, Ravi; Snyder, David S. "Bone marrow niche trafficking of miR-126 controls the self-renewal of leukemia stem cells in chronic myelogenous leukemia". Nature Medicine. 24 (4): 450–462. doi:10.1038/nm.4499. ISSN 1078-8956.
  20. ^ "kortylewski - Search Results - RWTH Publications". publications.rwth-aachen.de. Retrieved 2023-09-19.
  21. ^ Kortylewski, Marcin; Kujawski, Maciej; Wang, Tianhong; Wei, Sheng; Zhang, Shumin; Pilon-Thomas, Shari; Niu, Guilian; Kay, Heidi; Mulé, James; Kerr, William G; Jove, Richard; Pardoll, Drew; Yu, Hua. "Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity". Nature Medicine. 11 (12): 1314–1321. doi:10.1038/nm1325. ISSN 1078-8956.
  22. ^ Yu, Hua; Kortylewski, Marcin; Pardoll, Drew (2007-01-01). "Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment". Nature Reviews Immunology. 7 (1): 41–51. doi:10.1038/nri1995. ISSN 1474-1733.
  23. ^ Kortylewski, Marcin; Xin, Hong; Kujawski, Maciej; Lee, Heehyoung; Liu, Yong; Harris, Timothy; Drake, Charles; Pardoll, Drew; Yu, Hua. "Regulation of the IL-23 and IL-12 Balance by Stat3 Signaling in the Tumor Microenvironment". Cancer Cell. 15 (2): 114–123. doi:10.1016/j.ccr.2008.12.018. PMC 2673504. PMID 19185846.
  24. ^ Gao, Chan; Kozlowska, Anna; Nechaev, Sergey; Li, Haiqing; Zhang, Qifang; Hossain, Dewan M.S.; Kowolik, Claudia M.; Chu, Peiguo; Swiderski, Piotr; Diamond, Don J.; Pal, Sumanta K.; Raubitschek, Andrew; Kortylewski, Marcin (2013-12-15). "TLR9 Signaling in the Tumor Microenvironment Initiates Cancer Recurrence after Radiotherapy". Cancer Research. 73 (24): 7211–7221. doi:10.1158/0008-5472.CAN-13-1314. ISSN 0008-5472.
  25. ^ Minton, Kirsty. "Multi-tasking by STAT3". Nature Reviews Immunology. 9 (3): 149–149. doi:10.1038/nri2517. ISSN 1474-1733.
  26. ^ Kortylewski, Marcin; Swiderski, Piotr; Herrmann, Andreas; Wang, Lin; Kowolik, Claudia; Kujawski, Maciej; Lee, Heehyoung; Scuto, Anna; Liu, Yong; Yang, Chunmei; Deng, Jiehui; Soifer, Harris S; Raubitschek, Andrew; Forman, Stephen; Rossi, John J. "In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses". Nature Biotechnology. 27 (10): 925–932. doi:10.1038/nbt.1564. ISSN 1087-0156.
  27. ^ slater, elias (2014-02-18). "Delivering a Triple-Knockout Punch to Prostate Cancer". Prostate Cancer Foundation. Retrieved 2023-09-11.
  28. ^ Gantier, Michael P; Williams, Bryan R G. "siRNA delivery not Toll-free". Nature Biotechnology. 27 (10): 911–912. doi:10.1038/nbt1009-911. ISSN 1087-0156.
  29. ^ Kortylewski, Marcin; Moreira, Dayson. "Myeloid cells as a target for oligonucleotide therapeutics: turning obstacles into opportunities". Cancer Immunology, Immunotherapy. 66 (8): 979–988. doi:10.1007/s00262-017-1966-2. ISSN 0340-7004.
  30. ^ "STAT3 Inhibition Combined with CpG Immunostimulation Activates Antitumor Immunity to Eradicate Genetically Distinct Castration-Resistant Prostate Cancers". aacrjournals.org. Retrieved 2023-09-11.
  31. ^ Meyer, Sara E. (2020-01-16). "MicroRNA immunomodulating therapeutics". Blood. 135 (3): 155–156. doi:10.1182/blood.2019004106. ISSN 0006-4971.
  32. ^ "Scopus BioPharma Expands Immunotherapy Pipeline with Acquisition of Olimmune". www.sec.gov. Retrieved 2023-09-11.
  33. ^ Harris, William (2021-09-07). "Duet Therapeutics Appoints Marcin Kortylewski, Ph.D. as Senior Scientific Advisor". citybiz. Retrieved 2023-09-11.
  34. ^ Labant, MaryAnn (2014-06-15). "Therapeutic siRNA Interventions". Genetic Engineering & Biotechnology News. 34 (12): 1, 18–19. doi:10.1089/gen.34.12.01. ISSN 1935-472X.
  35. ^ Cell. "Molecular Therapy – Nucleic Acids editorial board contacts".
  36. ^ "Interview with Marcin Kortylewski, PhD". Oligonucleotide Therapeutics Society. 2020-01-27. Retrieved 2023-09-11.
  37. ^ "SITC Communications Committee". www.sitcancer.org. Retrieved 2023-09-11.
  38. ^ "Cancer Immunopathology and Immunotherapy Study Section".
  39. ^ "Outstanding New Investigator Awards | ASGCT - American Society of Gene & Cell Therapy | ASGCT - American Society of Gene & Cell Therapy". asgct.org. Retrieved 2023-09-04.
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