I feel privileged to be the Research Lead on M7824 at EMD Serono. I truly believe it will get approved for a number of indications and benefit cancer patients. This molecule has the potential to become the next immunotherapy anchor. It may also become the preferred combination partner, which will further improve the overall response rate, and give patients and HCP more treatment options and hope.
I feel privileged to be the Research Lead on M7824 at EMD Serono. I truly believe it will get approved for a number of indications and benefit cancer patients. This molecule has the potential to become the next immunotherapy anchor.
Senior Director in Translational Research, TIP ImmunoOncology
Joined Merck KGaA, Darmstadt, Germany: 1994
Key research fields and topics:
- Research Lead of M7824 Program
CV & Scientific activities
- M.D. Norman Bethune University of Medical Sciences, China
CV: Professional Career
CV: Professional Career
- 1980 - 1984
- Physician in Pediatrics and Clinical Virology, The Affiliated Hospital, China Medical University, Shenyang, China
- 1985 - 1986
- Research Fellow in Medical Virology, Institute of Virology, Chinese Academy of Preventive Medicine, Beijing, China
- 1985 - 1990
- Attending Physician in Pediatrics and Clinical Virology, The Affiliated Hospital, China Medical University, Shenyang, China
- 1990 - 1994
- Research Fellow in infectious Disease, Children’s Hospital, Harvard Medical School, Boston, MA
- since 1994
- Scientist in Molecular Biology, Group leader and Senior Scientist in - In Vivo Research, Associate Director in Discovery Pharmacology, Senior Director in ImmunoPharmacology Director in ImmunoPharmacology, EMD Serono Research & Development Institute Billerica, MA
- Led preclinical pharmacology group to generate the in vivo data package and delivered a total of 19 DP0 packages to support clinical trials
- Immunocytokines: KS-IL2, 14.18-IL2, BC1-IL12, Leu16-IL2, Selectikine, NHS-IL12
- Antibody fusion protein: anti-PD-L1/TGFb Trap, Fc-IFNb, Fc-EPO
- Antibodies: anti-IL6, anti-CD19, APERA (ADCC Potentiated EGFR Antibody), avelumab (anti-PD-L1)
- Vaccines: Tacemotide, Nanovacc
- TLR9 agonist
- TGFb RKI, Eg5 inhibitor
- DPTL for anti-CD19 (Phase I by CRUK)
- GPT member for Atacicept, Selectikine, avelumab, anti-PD-L1/TGFb Trap
- Most experienced GPT member in iONC; IND author (Module 2) for Selectikine, avelumab, anti-PD-L1/TGFb Trap
- Disciplined leader recognized for building a highly productive and reliable in vivo pharmacology team
- Mentored and developed two direct reports who have been promoted to Director and VP roles in pharma/biotech
- Lan Y et al, Enhanced pre-clinical anti-tumor activity of M7824, a novel bifunctional fusion protein simultaneously targeting PD-L1 and TGF-β. Science Translational Medicine. 2018 Jan 17;10(424).
- Xu C*, Zhang Y, Rolfe PA, Hernández VM, Guzman W, Kradjian G, Marelli B, Qin G, Qi J, Wang H, Yu H2, Tighe R, Lo KM, English JM, Radvanyi L, Lan Y*. Combination therapy with NHS-muIL12 and avelumab (anti-PD-L1) enhances antitumor efficacy in preclinical cancer models. Clin Cancer Res 2017 Oct 1;23(19):5869-5880.
- Waight, J.D., Takai, S., Marelli, B., Guozhong, Q., Hance, K.W., Zhang, D., Tighe, R., Lan, Y., Lo, K.-M., Sabzevari, H., Hofmeister, R., and Wilson, N.S. Epigenetic regulation of FoxP3 defines a homogenous population of stable CD4+ regulatory T cells in tumors from mice and humans. J. Immunol. 194:878-882, 2015.
- Fallon J, Tighe R, Kradjian G, Guzman W, Bernhardt A, Neuteboom B, Lan Y, Sabzevari H, Schlom J, Greiner JW.The immunocytokine NHS-IL12 as a potential cancer therapeutic. Oncotarget 2014 Apr 15 5(7):1869-84
- Gillies, S.D., Lan, Y., Hettmann, T., Brunkhorst, B., Sun, Y., Mueller S.O., and Lo, K.-M. A low-toxicity IL-2 based immunocytokine retains anti-tumor activity despite its high degree of IL-2 receptor selectivity. Clin. Cancer Res. 17:3673-85, 2011.
- Davis, J.H., Aperlo, C., Li, Y., Kurosawa, E., Lan, Y., Lo, K.-M., and Huston, J.S. SEEDbodies: Fusion proteins based on strand-exchange engineered domain (SEED) CH3 heterodimers in an Fc analogue platform for asymmetric binders or immunofusions and bispecific antibodies. Protein Engineering Design and Selection, 13:195-202, 2010.
- Kin-Ming Lo, Yan Lan, Scott Lauder, Jinyang Zhang, Beatrice Brunkhorst, Guozhong Qin, Rakesh Verma, Nigel Courtenay-Luck, and Stephen D. Gillies. huBC1-IL12, an immunocytokine which targets EDB-containing oncofetal fibronectin in tumors and tumor vasculature, shows potent anti-tumor activity in human tumor models. CancerImmunology Immunotherapy (2006).
- Stephen D. Gillies, Yan Lan, Steven Williams, Frank Carr, Andrew Raubitschek, and Kin-Ming Lo An anti-CD20-IL2 immunocytokine is highly efficacious in a SCID mouse model of established human B lymphoma. Blood 105:3972-3978 (2005).
- Jeffrey C. Way, Scott Lauder, Beatrice Brunkhorst, Su-Ming Kong, An Qi, Gordon Webster, Islay Campbell, Sue McKenzie, Yan Lan, Bo Marelli, Kin-Ming Lo, Stephen Gillies. Enhancement of Fc-erythropoietin pharmacokinetics through modification of disulfide bonds. Protein Engineering Design and Selection, 18:111-118 (2005).
- Kin-Ming Lo, Jinyang Zhang, Yaping Sun, Bo Morelli, Yan Lan, Scott Lauder, Bea Brunkhorst, Gordon Webster, Sophie Hallakou-Bozec, Lilliane Doaré, Stephen D. Gillies (2005) Engineering a pharmacologically superior form of leptin for the treatment of obesity. Protein Engineering Design and Selection, 18:1-10 (2005).
- Gillies, S.D., Lan, Y., Brunkhorst, B., Wong, W.-K., Li, Y., and Lo, K.-M. Bi-functional Cytokine Fusion Proteins for Gene Therapy and Antibody-targeted Treatment of Cancer. Cancer Immunol. Immunother. 51:449-460, 2002.
- Gillies, S.D., Lo, K.-M., Burger, C., Lan, Y., Dahl, T., and Wong W.-K. Improved Circulating Half-life and Efficacy of an Antibody-Interleukin 2 Immunocytokine Based on Reduced Intracellular Proteolysis. Clinical Cancer Research 8:210-216, 2002.
- Holden, S.A., Lan, Y., Pardo, A.M., Wesolowski, J.S., and Gillies, S.D. Augmentation of Antitumor Activity of an Antibody-Interleukin 2 Immunocytokine with Chemotherapeutic Agents. Clinical Cancer Research 7:2862-2869, 2001.
- Gillies, S.D., Lan, Y., Lo, K.-M., and Wesolowski, J.S. Improved efficacy of mouse antibody-cytokine fusion proteins in syngeneic mouse tumor models is due to their reduced immunogenicity. Proc. Am. Assoc. Cancer. Res. 40:658, 1999.
- Gillies, S.D., Lan, Y., Lo, K.-M., Super, M., and Wesolowski, J.S. Improving the Efficacy of Antibody-Interleukin 2 Fusion Proteins by Reducing their Interaction with Fc Receptors. Cancer Res. 59:2159-2166, 1999.
- Lin, L., Gillies, S.D., Lan, Y., Izotova, L., Wu, W., Schlom, J., and Pestka, S. Construction of Phosphorylatable Chimeric Monoclonal Antibody CC49. Int J Oncol 13:115-20, 1998.
- Gillies, S.D., Lan, Y., Wesolowski, J.S., Qian, X., Reisfeld, R.A., Holden, S., Super, M., and Lo, K.-M. Antibody-IL-12 Fusion Proteins Are Effective in SCID Mouse Models of Prostate and Colon Carcinoma Metastases. J. Immunol. 160:6195-6203, 1998.
- Lo, K.-M., Sudo, Y., Chen, J., Li, Y., Lan, Y., Kong, S.-M., Chen, L., An, Q., and Gillies, S.G. High Level Expression and Secretion of Fc-X Fusion Proteins in Mammalian Cells. Protein Engineering 11:495-500, 1998.
- Xiang, R., Lode, H.N., Dolman, C.S., Dreier, T., Varki, N.M., Qian, X., Lo, K.-M., Lan, Y., Super, M., Gillies, S.D., and Reisfeld, R.A. Elimination of Established Murine Colon Carcinoma Metastases by Antibody-Interleukin 2 Fusion Protein Therapy. Cancer Res. 57:4948-4955, 1997.
- Husson RN, Lan Y, Kojima E, Venzon D, Mitsuya H, McIntosh K. Vertical transmission of human immunodeficiency virus type 1: autologous neutralizing antibody, virus load, and virus phenotype. J Pediatr. 1995 Jun;126(6):865-71.
- Lan Y, Japour AJ, Kim S, Welles SL, Crumpacker CS, Cooper E, Al-Attar I, McIntosh K. A rapid, direct test for zidovudine susceptibility in clinical isolates of human immunodeficiency virus type 1 (HIV-1) from infected children. Clin Diagn Virol. 1995 Mar;3(3):259-71.
- Lan Y, Modern Clinical Virology, Chapter 29: Viral Pneumonia, ed. Tu P et al, People’s Health Press, Beijing China 1991
- Lan Y, et al, Detection of Adenovirus DNA in Throat Swab Specimens from Children with Acute Respiratory Infection by Nucleic Acid Hybridization. Chinese J. Expermental and Clinical Virology 4(2), 125-128 1990
- Lan Y, et al, Cloning of BamHI Digested Fragments of Adenovirus Type 3 Genome. Chinese J. Expermental and Clinical Virology 3(1), 87-89, 1989
- Lan Y, et al, Etiological Studies of Viral Pneumonia in Children in Shenyang from 1986-1987. Chinese J. Pediatrics, 27(2), 105-109 (1989)
- Lan Y, et al, Antiviral Effects of Curcuma Zedoaria on Influenza Virus and Parainfluenza Virus. J. Chinese Herbs, 41 (3), 109-110 (1988)
- Yu G X, Lan Y, et al Etiological Studies on Viral Pneumonia in Infants in Shenyang from 1977-1986. national Symposium on Acute Respiratory Diseases, pp85 (1987)
- Sun S, Lan Y et al, Preliminary Studies on Detecting Rotavirus Carrier in Healthy Children with ELISA and IEM. National Symposium on MoAb and ELISA, pp.101 (1984)
- Yu G.X, Lan Y, et al, Report on 27 cases of Respiratory Syncytia Viral Pneumonia in Infants. Compilation of Research Work in Public Health 217, 35-37 (1982)
ORAL and POSTER PRESENTATIONS
- Lan et al, Combination therapy with M7824 (MSB0011359C) and NHS-muIL12 enhances antitumor efficacy in preclinical cancer models. poster presentation in SITC, Nov 2018
- Lan et al, M7824 (MSB0011359C) is an effective combination partner with standard-of-care therapies in tumor models. poster presentation in SITC, Nov 2018
- Lan et al, Combination of M7824 (MSB0011359C) and radiation therapy enhances antitumor activity, increases immune response, and modulates radiation-induced fibrosis in cancer models. Poster presentation at ImmunoRAD, Sept 2018
- Lan et al, M7824, a Novel Bifunctional Fusion Protein Simultaneously Targeting PD-L1 and TGF-β, shows enhanced antitumor activities in preclinical models. Oral presentation at ICI Boston, March 2018
- Lan et al, Preclinical Evaluation and Mechanistic Characterization of M7824 (MSB0011359C), a Novel Bifunctional Fusion Protein Targeting the PD-L1 and TGF-β Pathways. AACR Annual Meeting 2017, Washington DC.
- Lan et al, Preclinical evaluation of M7824 (MSB0011359C), a novel bifunctional fusion protein targeting the PD-L1 and TGFβ pathways. Keystone Symposia: TGFβ in Immunity, Inflammation and Cancer, January 2017, Taos, NM.
- Xu C, Zhang Y, Kradjian G, Qin G, Qi J, Xu X, Marelli B, Yu H, Guzman W, Tighe R, Salazar R, Lo K-M, English J, Radvanyi L, Lan Y, Combination Therapy with NHS-muIL12 and Avelumab (anti-PD-L1) Enhances Antitumor Efficacy in Preclinical Cancer Models. SITC, Nov 2016.
PATENTS AND PATENT APPLICATIONS
- Lo, K.-M., and Lan, Y., Combination Therapy for Cancer (Utility filed 8/21/2017) Patent Status: Pending.
- Lan, Y., Combined inhibition of PD-1/PD-L1, TGFb and DNA-PK for the treatment of cancer, Patent Status: Pending
- Lan, Y. (coinventor) Treatment of Stage III NSCLC and mitigation of pathological conditions associated with treatment
- Gillies, S.D., Lo, K.-M., Lan, Y., and Verma, R. Interleukin-12 targeted to oncofetal fibronectin. US8420087, issued April 16, 2013.
- Gillies, S.D., Lo, K.-M., and Lan, Y. Heterodimeric fusion proteins useful for targeted immune therapy and general immune stimulation. US Patent 7,879,319, issued Feb 1, 2011.
- Gillies, S.D., Lan, Y., and Lo, K.-M. Heterodimeric fusion proteins useful for targeted immune therapy and general immune stimulation. US Patent Number 7,226,998, issued June 05, 2007.
- Gillies, S.D., Lan, Y., and Lo, K.-M. Heterodimeric fusion proteins useful for targeted immune therapy and general immune stimulation. US patent number- 6,838,260, issued Jan 04, 2005.
- Gillies, S.D., Lo, K.-M., and Lan, Y. Methods for enhancing the efficacy of IL-2 mediated immune responses. US20080025947 A1. Patent Status: Pending.
- Gillies, S.D., Lo, K.-M., and Lan, Y. Methods for enhancing the efficacy of IL-2 mediated immune responses. US20130017168 A1. Patent Status: Pending.
- Gillies, S.D., Lan, Y., and Holden, S. Enhancement of antibody-cytokine fusion protein mediated immune responses by combined treatment with immunocytokine uptake enhancing agents. US 20100297060 A1. Patent Status: Pending.
- Gillies, S.D., Lo, K.-M., Lan, Y., and Wesolowski, J. Enhancing the Circulating Half-Life of Antibody-based Fusion Proteins. US20060194952 A1. Patent Status: Pending.
- Gillies, S.D., Lo, K.-M., Lan, Y., and Wesolowski, J. Enhancing the Circulating Half-Life of Antibody-based Fusion Proteins. US20030105294 A1. Patent Status: Pending.