Herbert Lyerly

Overview:

Positions:

George Barth Geller Professor

Surgery, Surgical Sciences
School of Medicine

Professor of Surgery

Surgery, Surgical Sciences
School of Medicine

Professor in Immunology

Immunology
School of Medicine

Professor of Pathology

Pathology
School of Medicine

Affiliate,Duke Global Health Institute

Duke Global Health Institute
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Affiliate of the Regeneration Next Initiative

Regeneration Next Initiative
School of Medicine

Education:

M.D. 1983

University of California at Los Angeles

Grants:

Transfusion Medicine and Hematology

Administered By
Medicine, Hematology
Awarded By
National Institutes of Health
Role
Participating Faculty Member
Start Date
End Date

Developing Biomarker-Based Prognostics in Breast Cancer

Administered By
Surgery, Surgical Sciences
Awarded By
National Institutes of Health
Role
Consultant
Start Date
End Date

Immunotherapeutic Targeting of a Therapy Resistant Oncogenic HER2 Isoform

Administered By
Surgery, Surgical Sciences
Role
Co-Mentor
Start Date
End Date

Investigating Adaptive Immune Recognition of Dormant Disseminated Tumor Cells

Administered By
Surgery, Surgical Sciences
Role
Principal Investigator
Start Date
End Date

Mechanisms of Action and Resistance to PD-1 Immunotherapies in Breast Cancer

Administered By
Surgery, Surgical Sciences
Role
Collaborator
Start Date
End Date

Publications:

Abstract P2-09-16: CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients

Authors
Crosby, EJ; Gwin, WR; Chang, S; Maecker, HT; Lubkov, V; Snyder, JC; Broadwater, G; Hyslop, T; Osada, T; Hobeika, AC; Hartman, ZC; Morse, MA; Lyerly, HK
MLA Citation
Crosby, E. J., et al. “Abstract P2-09-16: CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients.” Poster Session Abstracts, American Association for Cancer Research, 2019. Crossref, doi:10.1158/1538-7445.sabcs18-p2-09-16.
URI
https://scholars.duke.edu/individual/pub1404161
Source
crossref
Published In
Poster Session Abstracts
Published Date
DOI
10.1158/1538-7445.sabcs18-p2-09-16

T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes.

T cell recognition of specific antigens mediates protection from pathogens and controls neoplasias, but can also cause autoimmunity. Our knowledge of T cell antigens and their implications for human health is limited by the technical limitations of T cell profiling technologies. Here, we present T-Scan, a high-throughput platform for identification of antigens productively recognized by T cells. T-Scan uses lentiviral delivery of antigen libraries into cells for endogenous processing and presentation on major histocompatibility complex (MHC) molecules. Target cells functionally recognized by T cells are isolated using a reporter for granzyme B activity, and the antigens mediating recognition are identified by next-generation sequencing. We show T-Scan correctly identifies cognate antigens of T cell receptors (TCRs) from viral and human genome-wide libraries. We apply T-Scan to discover new viral antigens, perform high-resolution mapping of TCR specificity, and characterize the reactivity of a tumor-derived TCR. T-Scan is a powerful approach for studying T cell responses.
Authors
Kula, T; Dezfulian, MH; Wang, CI; Abdelfattah, NS; Hartman, ZC; Wucherpfennig, KW; Lyerly, HK; Elledge, SJ
MLA Citation
Kula, Tomasz, et al. “T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes..” Cell, vol. 178, no. 4, Aug. 2019, pp. 1016-1028.e13. Pubmed, doi:10.1016/j.cell.2019.07.009.
URI
https://scholars.duke.edu/individual/pub1403283
PMID
31398327
Source
pubmed
Published In
Cell
Volume
178
Published Date
Start Page
1016
End Page
1028.e13
DOI
10.1016/j.cell.2019.07.009

Addressing the dichotomy between individual and societal approaches to personalised medicine in oncology.

Academic, industry, regulatory leaders and patient advocates in cancer clinical research met in November 2018 at the Innovation and Biomarkers in Cancer Drug Development meeting in Brussels to address the existing dichotomy between increasing calls for personalised oncology approaches based on individual molecular profiles and the need to make resource and regulatory decisions at the societal level in differing health-care delivery systems around the globe. Novel clinical trial designs, the utility and limitations of real-world evidence (RWE) and emerging technologies for profiling patient tumours and tumour-derived DNA in plasma were discussed. While randomised clinical trials remain the gold standard approach to defining clinical utility of local and systemic therapeutic interventions, the broader adoption of comprehensive tumour profiling and novel trial designs coupled with RWE may allow patient and physician autonomy to be appropriately balanced with broader assessments of safety and overall societal benefit.
Authors
Salgado, R; Solit, DB; Rimm, DL; Bogaerts, J; Canetta, R; Lively, T; Lyerly, K; Span, PN; Bateman-House, A; Makady, A; Bergmann, L; Nagai, S; Smith, C; Robson, M; Savage, M; Voest, E; Sweeney, C; Lambin, P; Thomas, M; Harris, L; Lacombe, D; Massard, C; IBCD-Faculty,
MLA Citation
Salgado, Roberto, et al. “Addressing the dichotomy between individual and societal approaches to personalised medicine in oncology..” Eur J Cancer, vol. 114, June 2019, pp. 128–36. Pubmed, doi:10.1016/j.ejca.2019.03.025.
URI
https://scholars.duke.edu/individual/pub1382955
PMID
31060925
Source
pubmed
Published In
Eur J Cancer
Volume
114
Published Date
Start Page
128
End Page
136
DOI
10.1016/j.ejca.2019.03.025

Identification of DK419, a potent inhibitor of Wnt/β-catenin signaling and colorectal cancer growth.

The Wnt signaling pathway is critical for normal tissue development and is an underlying mechanism of disease when dysregulated. Previously, we reported that the drug Niclosamide inhibits Wnt/β-catenin signaling by decreasing the cytosolic levels of Dishevelled and β-catenin, and inhibits the growth of colon cancers both in vitro and in vivo. Since the discovery of Niclosamide's anthelmintic activity, a growing body of literature indicates that Niclosamide is a multifunctional drug. In an effort to identify derivatives of Niclosamide with improved pharmacokinetic properties that maintain the multifunctional drug activity of Niclosamide for clinical evaluation, we designed DK419, a derivative containing a 1H-benzo[d]imidazole-4-carboxamide substructure, using the structure-activity relationships (SAR) of the Niclosamide salicylanilide chemotype. Similar to Niclosamide, we found DK419 inhibited Wnt/β-catenin signaling, altered cellular oxygen consumption rate and induced production of pAMPK. Moreover, we found DK419 inhibited the growth of CRC tumor cells in vitro, had good plasma exposure when dosed orally, and inhibited the growth of patient derived CRC240 tumor explants in mice dosed orally. DK419, a derivative of Niclosamide with multifunctional activity and improved pharmacokinetic properties, is a promising agent to treat colorectal cancer, Wnt-related diseases and other diseases in which Niclosamide has demonstrated functional activity.
Authors
Wang, J; Mook, RA; Ren, X-R; Zhang, Q; Jing, G; Lu, M; Spasojevic, I; Lyerly, HK; Hsu, D; Chen, W
MLA Citation
Wang, Jiangbo, et al. “Identification of DK419, a potent inhibitor of Wnt/β-catenin signaling and colorectal cancer growth..” Bioorg Med Chem, vol. 26, no. 20, Nov. 2018, pp. 5435–42. Pubmed, doi:10.1016/j.bmc.2018.09.016.
URI
https://scholars.duke.edu/individual/pub1353138
PMID
30274939
Source
pubmed
Published In
Bioorg Med Chem
Volume
26
Published Date
Start Page
5435
End Page
5442
DOI
10.1016/j.bmc.2018.09.016

Dendritic Cell/Cytokine-Induced Killer Cell Immunotherapy Combined with S-1 in Patients with Advanced Pancreatic Cancer: A Prospective Study.

Purpose: Advanced pancreatic cancer has remained challenging to treat effectively. This study aimed to investigate the clinical effects and safety of immunotherapy with dendritic cells and cytokine-induced killer cells (DC-CIK) administered with the chemotherapy (CT) S-1 in this malignancy.Experimental Design: Consecutive patients (n = 47) with advanced pancreatic cancer were treated with either DC-CIK + S-1, DC-CIK alone, S-1 alone, or best supportive care.Results: DC-CIK plus S-1 produced significantly longer median OS and PFS (212 and 136 days) compared with DC-CIK (128 and 85 days), CT (141 and 92 days), or supportive care only (52 and 43 days; P < 0.001). After adjusting for competing risk factors, DC-CIK combined with S-1 and receipt of 2 or more cycles of DC-CIK treatment remained independent predictors of disease-free and overall survival (P < 0.05). Phenotypic analysis of PBMCs demonstrated that the CD3+, CD3+/CD4+, and CD8+/CD28+ T-cell subsets were elevated (P < 0.05), while the CD3+/CD8+, CD3+/CD16+/CD56+ and CD4+/CD25+ cell subsets were significantly decreased after DC-CIK cell therapy (P < 0.05). There were no grade 3 or 4 toxicities. In addition, the mutational frequency in cell-free tumor DNA (cfDNA) declined in 4 of 14 patients who received DC-CIK, and was associated with a more favorable survival.Conclusions: Treatment of advanced pancreatic cancer with combined DC-CIK infusions and S-1 was safe, resulted in favorable PFS and OS, and modulated the peripheral blood immune repertoire. Clin Cancer Res; 23(17); 5066-73. ©2017 AACR.
Authors
Jiang, N; Qiao, G; Wang, X; Morse, MA; Gwin, WR; Zhou, L; Song, Y; Zhao, Y; Chen, F; Zhou, X; Huang, L; Hobeika, A; Yi, X; Xia, X; Guan, Y; Song, J; Ren, J; Lyerly, HK
MLA Citation
Jiang, Ni, et al. “Dendritic Cell/Cytokine-Induced Killer Cell Immunotherapy Combined with S-1 in Patients with Advanced Pancreatic Cancer: A Prospective Study..” Clin Cancer Res, vol. 23, no. 17, Sept. 2017, pp. 5066–73. Pubmed, doi:10.1158/1078-0432.CCR-17-0492.
URI
https://scholars.duke.edu/individual/pub1259304
PMID
28611200
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
23
Published Date
Start Page
5066
End Page
5073
DOI
10.1158/1078-0432.CCR-17-0492