Overview
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Overview
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Laboratory Introduction
Laboratory Introduction
Laboratory for Biologic Therapy of Cancer (LBTC)
Laboratory for Biologic Therapy of Cancer (LBTC)
Research Focus 1. Targeted Therapy for Lung Cancer, Malignant Lymphoma, and Head & Neck Cancer 2. Cancer immunotherapy and tumor immunology Our research is focused on discovering actionable targets as well as genetic alterations associated with acquired resistance to targeted therapy for lung cancer, malignant lymphoma, and head & neck cancer. Biologic therapy shows anti-tumor effects primarily through the action of natural host defense mechanisms or the administration of natural mammalian substances. We have been working on the development of a new strategy by modulation of the immune response against cancer. Our fundamental studies are translational research and immunotherapy-enhancing research.
Related Researcher
Dong-Wan Kim Professor
- Email : kimdw@snu.ac.kr
Tae Min Kim Professor
- Email : gabriel9@snu.ac.kr
Bhumsuk Keam Professor
- Email : bhumsuk@snu.ac.kr
Mi So Kim Professor
- Email : misokim@snu.ac.kr
Jeonghwan Youk Professor
- Email : jhyouk@snu.ac.kr
Research topics
Targeted Therapy for Lung Cancer, Malignant Lymphoma, and Head & Neck Cancer Identification of a novel mutation and its function within new target associated with chemo-resistance. We also evaluate the tumor signaling pathway associated with chemo-resistance and establish novel treatment strategies to overcome chemo-resistance. In our laboratory, tumor tissue or body fluids are obtained from cancer patients before and after targeted therapy to study the mechanism of resistance to targeted therapy. In addition, a patient-derived cancer cell line as well as organoid is established through the collaboration with Korean Cell Line Bank. Thereafter, a genetic alteration associated with acquired resistance is induced in an in vitro model and chemo-resistance mechanism is identified through an unbiased approach using next-generation sequencing and functional genomic methods. Cancer Immunotherapy Immune checkpoint blockade such as CTLA4 and PD-1/PD-L1 inhibitors is standard treatment for melanoma, lung cancer, and various cancer subtypes. We are monitoring immune profiles including immune cells or cytokines during immune checkpoint blockade. In addition, we are evaluating a biomarker associated with response and resistance to immune checkpoint blockade. Our laboratory has developed a new method for NK cell expansion and performed the adoptive transfer trial of allogeneic NK cells in advanced cancer patients to enhance the anti-tumor efficacy of immunotherapy. The first clinical trial of HLA mismatched (haploidentical) allogeneic NK cell therapy (MG4101) was performed in 2009 (NCT01212341). In addition, we have established an immunotherapy-enhancing strategy in combination with targeted therapy or novel immunotherapy and translated this knowledge into a new clinical trial.
Research goals
- Targeted Therapy for Lung Cancer, Malignant Lymphoma, and Head & Neck Cancer
- Cancer immunotherapy and tumor immunology
Research achievements
Lee J, Keam B, Kim S, Heo JN, Joung E, Kim M, Kim TM, Kim DW, Heo DS. The antitumor activity of a novel GCN2 inhibitor in head and neck squamous cell carcinoma cell lines. Transl Oncol. 2023 Jan;27:101592. doi: 10.1016/j.tranon.2022.101592. Epub 2022 Nov 24.
Lee J, Keam B, Park HR, Park JE, Kim S, Kim M, Kim TM, Kim DW, Heo DS. Monalizumab efficacy correlates with HLA-E surface expression and NK cell activity in head and neck squamous carcinoma cell lines. J Cancer Res Clin Oncol. 2022 Dec 22. doi: 10.1007/s00432-022-04532-x. Online ahead of print.
Park HR, Kim SE, Keam B, Chung H, Seok SH, Kim S, Kim M, Kim TM, Doh J, Kim DW, Heo DS. Blockade of CD47 enhances the antitumor effect of macrophages in renal cell carcinoma through trogocytosis. Sci Rep. 2022 Jul 22;12(1):12546. doi: 10.1038/s41598-022-16766-3.
Lee C, Kim M, Kim DW, Kim TM, Kim S, Im SW, Jeon YK, Keam B, Ku JL, Heo DS. Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non-Small Cell Lung Cancer. Cancer Res Treat. 2022 Jan;54(1):140-149. doi: 10.4143/crt.2021.385. Epub 2021 May 3.
Park HR, Kim TM, Lee Y, Kim S, Park S, Ju YS, Kim M, Keam B, Jeon YK, Kim DW, Heo DS. Acquired Resistance to Third-Generation EGFR Tyrosine Kinase Inhibitors in Patients With De Novo EGFRT790M-Mutant NSCLC. J Thorac Oncol. 2021 Nov;16(11):1859-1871. doi: 10.1016/j.jtho.2021.06.013. Epub 2021 Jul 6.
Park S, Kim TM, Cho SY, Kim S, Oh Y, Kim M, Keam B, Kim DW, Heo DS. Combined blockade of polo-like kinase and pan-RAF is effective against NRAS-mutant non-small cell lung cancer cells. Cancer Lett. 2020 Sep 23;495:135-144.
Park JE, Kim SE, Keam B, Park HR, Kim S, Kim M, Kim TM, Doh J, Kim DW, Heo DS. Anti-tumor effects of NK cells and anti-PD-L1 antibody with antibody-dependent cellular cytotoxicity in PD-L1-positive cancer cell lines. J Immunother Cancer. 2020 Aug;8(2):e000873.
Lee Y, Kim TM, Kim DW, Kim S, Kim M, Keam B, Ku JL, Heo DS. Pre-clinical Modeling of Osimertinib for Non-small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations. J Thorac Oncol. 2019 Sep;14(9):1556-1566.
Park HR, Ahn YO, Kim TM, Kim S, Kim S, Lee YS, Kim M, Keam B, Kim DW, Heo DS. NK92-CD16 cells are cytotoxic to non-small cell lung cancer cell lines that have acquired resistance to tyrosine kinase inhibitors. Cytotherapy. 2019 Jun;21(6):603-611.
Jung M, Kim S, Lee JK, Yoon SO, Park HS, Hong SW, Park WS, Kim JE, Kim J, Keam B, Kim HJ, Kang HJ, Kim DW, Jung KC, Kim YT, Heo DS, Kim TM, Jeon YK. Clinicopathological and Preclinical Findings of NUT Carcinoma: A Multicenter Study. Oncologist. 2019 Jan 29. [Epub ahead of print]
Kim SJ, Kim S, Kim DW, Kim M, Keam B, Kim TM, Lee Y, Koh J, Jeon YK, Heo DS. Alterations in PD-L1 Expression Associated with Acquisition of Resistance to ALK Inhibitors in ALK-Rearranged Lung Cancer. Cancer Res Treat. Cancer Res Treat. 2019 Jul;51(3):1231-1240.
Kim S, Kim TM, Kim DW, Kim S, Kim M, Ahn YO, Keam B, Heo DS. Acquired Resistance of MET-Amplified Non-small Cell Lung Cancer Cells to the MET Inhibitor Capmatinib. Cancer Res Treat. Cancer Res Treat. 2019 Jul;51(3):951-962.
Lee J, Keam B, Park HR, Park JE, Kim S, Kim M, Kim TM, Kim DW, Heo DS. Monalizumab efficacy correlates with HLA-E surface expression and NK cell activity in head and neck squamous carcinoma cell lines. J Cancer Res Clin Oncol. 2022 Dec 22. doi: 10.1007/s00432-022-04532-x. Online ahead of print.
Park HR, Kim SE, Keam B, Chung H, Seok SH, Kim S, Kim M, Kim TM, Doh J, Kim DW, Heo DS. Blockade of CD47 enhances the antitumor effect of macrophages in renal cell carcinoma through trogocytosis. Sci Rep. 2022 Jul 22;12(1):12546. doi: 10.1038/s41598-022-16766-3.
Lee C, Kim M, Kim DW, Kim TM, Kim S, Im SW, Jeon YK, Keam B, Ku JL, Heo DS. Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non-Small Cell Lung Cancer. Cancer Res Treat. 2022 Jan;54(1):140-149. doi: 10.4143/crt.2021.385. Epub 2021 May 3.
Park HR, Kim TM, Lee Y, Kim S, Park S, Ju YS, Kim M, Keam B, Jeon YK, Kim DW, Heo DS. Acquired Resistance to Third-Generation EGFR Tyrosine Kinase Inhibitors in Patients With De Novo EGFRT790M-Mutant NSCLC. J Thorac Oncol. 2021 Nov;16(11):1859-1871. doi: 10.1016/j.jtho.2021.06.013. Epub 2021 Jul 6.
Park S, Kim TM, Cho SY, Kim S, Oh Y, Kim M, Keam B, Kim DW, Heo DS. Combined blockade of polo-like kinase and pan-RAF is effective against NRAS-mutant non-small cell lung cancer cells. Cancer Lett. 2020 Sep 23;495:135-144.
Park JE, Kim SE, Keam B, Park HR, Kim S, Kim M, Kim TM, Doh J, Kim DW, Heo DS. Anti-tumor effects of NK cells and anti-PD-L1 antibody with antibody-dependent cellular cytotoxicity in PD-L1-positive cancer cell lines. J Immunother Cancer. 2020 Aug;8(2):e000873.
Lee Y, Kim TM, Kim DW, Kim S, Kim M, Keam B, Ku JL, Heo DS. Pre-clinical Modeling of Osimertinib for Non-small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations. J Thorac Oncol. 2019 Sep;14(9):1556-1566.
Park HR, Ahn YO, Kim TM, Kim S, Kim S, Lee YS, Kim M, Keam B, Kim DW, Heo DS. NK92-CD16 cells are cytotoxic to non-small cell lung cancer cell lines that have acquired resistance to tyrosine kinase inhibitors. Cytotherapy. 2019 Jun;21(6):603-611.
Jung M, Kim S, Lee JK, Yoon SO, Park HS, Hong SW, Park WS, Kim JE, Kim J, Keam B, Kim HJ, Kang HJ, Kim DW, Jung KC, Kim YT, Heo DS, Kim TM, Jeon YK. Clinicopathological and Preclinical Findings of NUT Carcinoma: A Multicenter Study. Oncologist. 2019 Jan 29. [Epub ahead of print]
Kim SJ, Kim S, Kim DW, Kim M, Keam B, Kim TM, Lee Y, Koh J, Jeon YK, Heo DS. Alterations in PD-L1 Expression Associated with Acquisition of Resistance to ALK Inhibitors in ALK-Rearranged Lung Cancer. Cancer Res Treat. Cancer Res Treat. 2019 Jul;51(3):1231-1240.
Kim S, Kim TM, Kim DW, Kim S, Kim M, Ahn YO, Keam B, Heo DS. Acquired Resistance of MET-Amplified Non-small Cell Lung Cancer Cells to the MET Inhibitor Capmatinib. Cancer Res Treat. Cancer Res Treat. 2019 Jul;51(3):951-962.
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