Herbert Lyerly

Overview:

Positions:

George Barth Geller Distinguished Professor of Immunology

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

Core Faculty Member, Duke-Margolis Center for Health Policy

Duke - Margolis Center For Health Policy
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 - Los Angeles

Grants:

A Cancer Rainbow Mouse for the Simultaneous Assessment of Multiple Oncogenes

Administered By
Cell Biology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

A Molecular Framework for Understanding DCIS

Awarded By
Department of Defense
Role
Principal Investigator
Start Date
End Date

Advancing Immunology in Dogs with Naturally-occurring Invasive Bladder Cancer, a Relevant Model to Improve Immunotherapy Across Molecular Cancer Subtypes in Humans

Awarded By
Purdue University
Role
Principal Investigator
Start Date
End Date

Preclinical Development Of Rna Decoys

Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

Administrative Supplement for Recruitment of New Faculty

Administered By
Duke Cancer Institute
Awarded By
National Cancer Institute
Role
Principal Investigator
Start Date
End Date

Publications:

An age-independent gene signature for monitoring acute rejection in kidney transplantation.

Acute rejection (AR) remains a significant problem that negatively impacts long-term renal allograft survival. Numerous therapies are used to prevent AR that differ by center and recipient age. This variability confounds diagnostic methods. Methods: To develop an age-independent gene signature for AR effective across a broad array of immunosuppressive regimens, we compiled kidney transplant biopsy (n=1091) and peripheral blood (n=392) gene expression profiles from 12 independent public datasets. After removing genes differentially expressed in pediatric and adult patients, we compared gene expression profiles from biopsy and peripheral blood samples of patients with AR to those who were stable (STA), using Mann-Whitney U Tests with validation in independent testing datasets. We confirmed this signature in pediatric and adult patients (42 AR and 47 STA) from our institutional biorepository. Results: We identified a novel age-independent gene network that identified AR from both kidney and blood samples. We developed a 90-probe set signature targeting 76 genes that differentiated AR from STA and found an 8 gene subset (DIP2C, ENOSF1, FBXO21, KCTD6, PDXDC1, REXO2, HLA-E, and RAB31) that was associated with AR. Conclusion: We used publicly available datasets to create a gene signature of AR that identified AR irrespective of immunosuppression regimen or recipient age. This study highlights a novel model to screen and validate biomarkers across multiple treatment regimens.
Authors
Shaw, BI; Cheng, DK; Acharya, CR; Ettenger, RB; Lyerly, HK; Cheng, Q; Kirk, AD; Chambers, ET
MLA Citation
Shaw, Brian I., et al. “An age-independent gene signature for monitoring acute rejection in kidney transplantation.Theranostics, vol. 10, no. 15, 2020, pp. 6977–86. Pubmed, doi:10.7150/thno.42110.
URI
https://scholars.duke.edu/individual/pub1447710
PMID
32550916
Source
pubmed
Published In
Theranostics
Volume
10
Published Date
Start Page
6977
End Page
6986
DOI
10.7150/thno.42110

Stimulation of Oncogene-Specific Tumor-Infiltrating T Cells through Combined Vaccine and αPD-1 Enable Sustained Antitumor Responses against Established HER2 Breast Cancer.

PURPOSE:Despite promising advances in breast cancer immunotherapy, augmenting T-cell infiltration has remained a significant challenge. Although neither individual vaccines nor immune checkpoint blockade (ICB) have had broad success as monotherapies, we hypothesized that targeted vaccination against an oncogenic driver in combination with ICB could direct and enable antitumor immunity in advanced cancers. EXPERIMENTAL DESIGN:Our models of HER2+ breast cancer exhibit molecular signatures that are reflective of advanced human HER2+ breast cancer, with a small numbers of neoepitopes and elevated immunosuppressive markers. Using these, we vaccinated against the oncogenic HER2Δ16 isoform, a nondriver tumor-associated gene (GFP), and specific neoepitopes. We further tested the effect of vaccination or anti-PD-1, alone and in combination. RESULTS:We found that only vaccination targeting HER2Δ16, a driver of oncogenicity and HER2-therapeutic resistance, could elicit significant antitumor responses, while vaccines targeting a nondriver tumor-specific antigen or tumor neoepitopes did not. Vaccine-induced HER2-specific CD8+ T cells were essential for responses, which were more effective early in tumor development. Long-term tumor control of advanced cancers occurred only when HER2Δ16 vaccination was combined with αPD-1. Single-cell RNA sequencing of tumor-infiltrating T cells revealed that while vaccination expanded CD8 T cells, only the combination of vaccine with αPD-1 induced functional gene expression signatures in those CD8 T cells. Furthermore, we show that expanded clones are HER2-reactive, conclusively demonstrating the efficacy of this vaccination strategy in targeting HER2. CONCLUSIONS:Combining oncogenic driver targeted vaccines with selective ICB offers a rational paradigm for precision immunotherapy, which we are clinically evaluating in a phase II trial (NCT03632941).
Authors
Crosby, EJ; Acharya, CR; Haddad, A-F; Rabiola, CA; Lei, G; Wei, J-P; Yang, X-Y; Wang, T; Liu, C-X; Wagner, KU; Muller, WJ; Chodosh, LA; Broadwater, G; Hyslop, T; Shepherd, JH; Hollern, DP; He, X; Perou, CM; Chai, S; Ashby, BK; Vincent, BG; Snyder, JC; Force, J; Morse, MA; Lyerly, HK; Hartman, ZC
MLA Citation
Crosby, Erika J., et al. “Stimulation of Oncogene-Specific Tumor-Infiltrating T Cells through Combined Vaccine and αPD-1 Enable Sustained Antitumor Responses against Established HER2 Breast Cancer.Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, July 2020. Epmc, doi:10.1158/1078-0432.ccr-20-0389.
URI
https://scholars.duke.edu/individual/pub1453955
PMID
32732224
Source
epmc
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Published Date
DOI
10.1158/1078-0432.ccr-20-0389

Novel Therapeutic Interventions Early in the Disease Trajectory: Drug Development Beyond the Refractory Setting.

The 2019 Accelerating Anticancer Agent Development (AAADV) Workshop assembled a panel of experts for an in-depth discussion session to present "Novel Therapeutic Interventions Early in the Disease Trajectory." The panel reviewed the limitations of evaluating investigational cancer therapeutics solely in advanced metastatic and relapsed/refractory disease settings, and recommended strategies for drug evaluation earlier in the disease course, including in the first line in combination with standard chemotherapy and in the maintenance and neoadjuvant disease settings. Advantages of earlier drug evaluation were discussed, including expanding the population of evaluable patients, earlier response assessment via surrogate endpoints, earlier clinical benefit in the disease course, tailoring of therapies based on response, and furthering our understanding of biomarker-driven therapies.
Authors
Hafez, N; Rugo, HS; Tempero, MA; Fox, E; Reaman, GH; Lyerly, HK; Walker, D; LoRusso, PM
MLA Citation
Hafez, Navid, et al. “Novel Therapeutic Interventions Early in the Disease Trajectory: Drug Development Beyond the Refractory Setting.Clin Cancer Res, June 2020. Pubmed, doi:10.1158/1078-0432.CCR-19-4035.
URI
https://scholars.duke.edu/individual/pub1448029
PMID
32571790
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Published Date
DOI
10.1158/1078-0432.CCR-19-4035

HER2-LAMP vaccines effectively traffic to endolysosomal compartments and generate enhanced polyfunctional T cell responses that induce complete tumor regression.

BACKGROUND: The advent of immune checkpoint blockade antibodies has demonstrated that effective mobilization of T cell responses can cause tumor regression of metastatic cancers, although these responses are heterogeneous and restricted to certain histologic types of cancer. To enhance these responses, there has been renewed emphasis in developing effective cancer-specific vaccines to stimulate and direct T cell immunity to important oncologic targets, such as the oncogene human epidermal growth factor receptor 2 (HER2), expressed in ~20% of breast cancers (BCs). METHODS: In our study, we explored the use of alternative antigen trafficking through use of a lysosome-associated membrane protein 1 (LAMP) domain to enhance vaccine efficacy against HER2 and other model antigens in both in vitro and in vivo studies. RESULTS: We found that inclusion of this domain in plasmid vaccines effectively trafficked antigens to endolysosomal compartments, resulting in enhanced major histocompatibility complex (MHC) class I and II presentation. Additionally, this augmented the expansion/activation of antigen-specific CD4+ and CD8+ T cells and also led to elevated levels of antigen-specific polyfunctional CD8+ T cells. Significantly, vaccination with HER2-LAMP produced tumor regression in ~30% of vaccinated mice with established tumors in an endogenous model of metastatic HER2+ BC, compared with 0% of HER2-WT vaccinated mice. This therapeutic benefit is associated with enhanced tumor infiltration of activated CD4+ and CD8+ T cells. CONCLUSIONS: These data demonstrate the potential of using LAMP-based endolysosomal trafficking as a means to augment the generation of polyfunctional, antigen-specific T cells in order to improve antitumor therapeutic responses using cancer antigen vaccines.
Authors
Chen, AC; Xu, R; Wang, T; Wei, J; Yang, X-Y; Liu, C-X; Lei, G; Lyerly, HK; Heiland, T; Hartman, ZC
MLA Citation
Chen, Alan Chen, et al. “HER2-LAMP vaccines effectively traffic to endolysosomal compartments and generate enhanced polyfunctional T cell responses that induce complete tumor regression.J Immunother Cancer, vol. 8, no. 1, June 2020. Pubmed, doi:10.1136/jitc-2019-000258.
URI
https://scholars.duke.edu/individual/pub1447972
PMID
32532838
Source
pubmed
Published In
Journal for Immunotherapy of Cancer
Volume
8
Published Date
DOI
10.1136/jitc-2019-000258

Patient-Reported Outcomes in Oncology Clinical Trials: Stakeholder Perspectives from the Accelerating Anticancer Agent Development and Validation Workshop 2019.

Authors
Bhatnagar, V; Hudgens, S; Piault-Louis, E; Jones, L; Beaver, JA; Lyerly, HK; Reaman, G; Fleming, T; Kluetz, PG
MLA Citation
URI
https://scholars.duke.edu/individual/pub1447261
PMID
32463153
Source
pubmed
Published In
Oncologist
Published Date
DOI
10.1634/theoncologist.2020-0062