Herbert Lyerly

Overview:

Positions:

George Barth Geller Distinguished 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:

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

Inhibition of Wnt/B-Catenin Signaling in Colorectal Cancer Therapy

Administered By
Medicine, Gastroenterology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

A Molecular Framework for Understanding DCIS

Administered By
Surgery, Surgical Sciences
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

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

Preclinical Development Of Rna Decoys

Administered By
Surgery, Surgical Sciences
Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

Publications:

A cancer rainbow mouse for visualizing the functional genomics of oncogenic clonal expansion.

Field cancerization is a premalignant process marked by clones of oncogenic mutations spreading through the epithelium. The timescales of intestinal field cancerization can be variable and the mechanisms driving the rapid spread of oncogenic clones are unknown. Here we use a Cancer rainbow (Crainbow) modelling system for fluorescently barcoding somatic mutations and directly visualizing the clonal expansion and spread of oncogenes. Crainbow shows that mutations of ß-catenin (Ctnnb1) within the intestinal stem cell results in widespread expansion of oncogenes during perinatal development but not in adults. In contrast, mutations that extrinsically disrupt the stem cell microenvironment can spread in adult intestine without delay. We observe the rapid spread of premalignant clones in Crainbow mice expressing oncogenic Rspondin-3 (RSPO3), which occurs by increasing crypt fission and inhibiting crypt fixation. Crainbow modelling provides insight into how somatic mutations rapidly spread and a plausible mechanism for predetermining the intratumor heterogeneity found in colon cancers.
Authors
Boone, PG; Rochelle, LK; Ginzel, JD; Lubkov, V; Roberts, WL; Nicholls, PJ; Bock, C; Flowers, ML; von Furstenberg, RJ; Stripp, BR; Agarwal, P; Borowsky, AD; Cardiff, RD; Barak, LS; Caron, MG; Lyerly, HK; Snyder, JC
MLA Citation
Boone, Peter G., et al. “A cancer rainbow mouse for visualizing the functional genomics of oncogenic clonal expansion..” Nat Commun, vol. 10, no. 1, Dec. 2019. Pubmed, doi:10.1038/s41467-019-13330-y.
URI
https://scholars.duke.edu/individual/pub1423128
PMID
31792216
Source
pubmed
Published In
Nature Communications
Volume
10
Published Date
Start Page
5490
DOI
10.1038/s41467-019-13330-y

Predictive significance of T cell subset changes during ex vivo generation of adoptive cellular therapy products for the treatment of advanced non-small cell lung cancer.

Adoptive T cell immunotherapy with cytokine-induced killer cells (CIKs) has been demonstrated to prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate whether the expansion of effector T cells and the decrease of regulatory T cells (Tregs) that occurred during the ex vivo generation of DC-CIKs were associated with improved clinical outcome in patients who received treatment. CIKs were generated ex vivo over a 28-day period from the peripheral blood apheresis product of 163 patients with advanced cancer (including 30 with NSCLC). CIKs were also generated from an additional cohort of 65 patients with NSCLC over a 15-day period. The progression-free survival (PFS) and overall survival (OS) time of patients treated with CIKs was determined by reviewing the patients' medical records. The number of CIKs gradually increased during the culture period and peaked at day 15, followed by a slight decline until day 28. Similarly, the percentages of T cell subtypes associated with anti-tumor activity (CD3+, CD3+CD4+, CD3+CD8+ and CD8+CD28+) peaked at day 15. Although the percentage of CD4+CD25+CD127+ Tregs increased by day 7, a decrease was subsequently observed. Among the 95 patients with NSCLC, those with a post/pre-culture ratio of CD8+CD28+ T lymphocytes >2.2 had significantly better PFS and OS compared with those with ratios ≤2.2. Those with a post/pre-culture CD4+CD25+CD127+ Treg ratio ≤0.6 had significantly better OS and PFS compared with those with ratios >0.6. The peak expansion of CIKs from peripheral blood mononuclear cells occurred at day 15 of ex vivo culture. PFS and OS were associated with post/pre-culture CD8+CD28+ T lymphocyte ratio >2.2 and post/pre-culture CD4+CD25+CD127+ Treg ratio <0.6 in the CIKs of patients with advanced NSCLC treated with adoptive T cell immunotherapy. Further efforts are underway to optimize the DC-CIK infusion for cancer immunotherapy.
Authors
MLA Citation
Huang, Lefu, et al. “Predictive significance of T cell subset changes during ex vivo generation of adoptive cellular therapy products for the treatment of advanced non-small cell lung cancer..” Oncol Lett, vol. 18, no. 6, Dec. 2019, pp. 5717–24. Pubmed, doi:10.3892/ol.2019.10964.
URI
https://scholars.duke.edu/individual/pub1423209
PMID
31788044
Source
pubmed
Published In
Oncology Letters
Volume
18
Published Date
Start Page
5717
End Page
5724
DOI
10.3892/ol.2019.10964

GEOGRAPHIC DISPARITIES IN LIFE EXPECTANCY AND MORTALITY IN THE U.S.

AbstractAlthough the US has one of the highest per-capita health expenditures in the world, it noticeably lags behind a number of other industrialized countries in terms of life expectancy (LE). These disparities remain unexplained by individual demographic, socioeconomic, and healthcare factors. Analysis of death certificates for 1999-2016 revealed that diseases contributed most to LE variability are myocardial infarction (explained 12.9% of the difference in mortality), heart failure (10.6%), stroke (8.2%), lung cancer (7.5%) and COPD (7.2%). Analysis of histories of diseased patients in Medicare records showed that septicemia (15.7%), low weight (13.8%), renal disease (13.3%), disorders of electrolyte and fluid balance (9.0%) and heart failure (7.3%) contributed most to the disparities. Diseases that substantially contribute to disparities in LE in the US include both common and less-often-discussed diseases. Future studies of variations in treatment patterns, access-to and quality-of medical care for these diseases could provide important insight in observed patterns.
Authors
Kravchenko, J; Lyerly, HK
MLA Citation
Kravchenko, Julia, and H. Kim Lyerly. “GEOGRAPHIC DISPARITIES IN LIFE EXPECTANCY AND MORTALITY IN THE U.S..” Innovation in Aging, vol. 3, no. Suppl 1, Nov. 2019, pp. S427–S427. Epmc, doi:10.1093/geroni/igz038.1597.
URI
https://scholars.duke.edu/individual/pub1424220
Source
epmc
Published In
Innovation in Aging
Volume
3
Published Date
Start Page
S427
End Page
S427
DOI
10.1093/geroni/igz038.1597

Immune correlates of clinical benefit in a phase I study of hyperthermia with adoptive T cell immunotherapy in patients with solid tumors.

Purpose: To characterize the T cell receptor (TCR) repertoire, serum cytokine levels, peripheral blood T lymphocyte populations, safety, and clinical efficacy of hyperthermia (HT) combined with autologous adoptive cell therapy (ACT) and either salvage chemotherapy (CT) or anti-PD-1 antibody in patients with previously treated advanced solid tumors.Materials and methods: Thirty-three (33) patients with ovarian, pancreatic, gastric, colorectal, cervical, or endometrial cancer were recruited into the following therapeutic groups: HT + ACT (n = 10), HT + ACT + anti-PD-1 inhibitor (pembrolizumab) (n = 11) and HT + ACT + CT (n = 12). Peripheral blood was collected to analyze TCR repertoire, measurements of cytokines levels and lymphocyte sub-populations before and after treatment.Results: The objective response rate (ORR) was 30% (10/33), including three complete responses (CR) (9.1%) and seven partial responses (PR) (21.2%) and a disease control rate (DCR = CR + PR + SD) of 66.7% (22 of 33). The most common adverse reactions, blistering, subcutaneous fat induration, local heat-related pain, vomiting and sinus tachycardia, were observed in association with HT. IL-2, IL-4, TNF-α, and IFN-γ levels in peripheral blood were significantly increased among the clinical responders (p < 0.05) while IL-6 and IL-10 were elevated among those with progressive disease (p < 0.05). Peripheral blood CD8+/CD28+ T cells increased (p = 0.002), while the CD4+/CD25+/CD127+Treg cells decreased after therapy (p = 0.012). TCR diversity was substantially increased among the clinical responders.Conclusions: Combining HT with ACT plus either CT or anti-PD-1 antibody was safe, generated clinical responses in previously treated advanced cancers, and promoted TCR repertoire diversity and favorable changes in serum IL-2, IL-4, TNF-α, and IFN-γ levels in clinical responders.
Authors
Qiao, G; Wang, X; Zhou, X; Morse, MA; Wu, J; Wang, S; Song, Y; Jiang, N; Zhao, Y; Zhou, L; Zhao, J; Di, Y; Zhu, L; Hobeika, A; Ren, J; Lyerly, HK
MLA Citation
Qiao, Guoliang, et al. “Immune correlates of clinical benefit in a phase I study of hyperthermia with adoptive T cell immunotherapy in patients with solid tumors..” Int J Hyperthermia, vol. 36, no. sup1, Nov. 2019, pp. 74–82. Pubmed, doi:10.1080/02656736.2019.1647350.
URI
https://scholars.duke.edu/individual/pub1423203
PMID
31795830
Source
pubmed
Published In
Int J Hyperthermia
Volume
36
Published Date
Start Page
74
End Page
82
DOI
10.1080/02656736.2019.1647350

Adoptive immunotherapy with autologous T-cell infusions reduces opioid requirements in advanced cancer patients.

Relief of cancer-related pain remains challenging despite the availability of a range of opioid and nonopioid medications. Animal models demonstrate that T lymphocytes may mediate analgesia by producing endogenous opioids, but definitive clinical data are limited. Transfer of ex vivo adoptive cellular therapy (ACT) is being tested as an anticancer therapy. We retrospectively reviewed the medical charts of 357 patients with various malignancies who received 3 intravenous infusions of autologous cytokine-activated T-cell-enriched products. Among these were 55 patients who required opioids for moderate or severe cancer-related pain. Opioid dosage and cancer pain score were recorded daily for 2 consecutive weeks before and 2 weeks after the ACT infusions. The average oral morphine equivalent doses and cancer pain scores were significantly decreased after the ACT infusions. The proportion of patients with breakthrough pain also declined. Moreover, higher frequencies of expanded CD3, CD3/CD4, and CD3/CD8 T cells within the ACT product were associated with favorable analgesic effects. Transient elevations in CD3 and CD3/CD8T-cell subpopulations and decreases in CD4CD25 Treg were observed in patients' blood after the ACT. In conclusion, ACT was capable of reducing cancer pain severity and opioid consumption and favorably modulating peripheral blood T-cell populations.
Authors
Zhou, X; Qiao, G; Ren, J; Wang, X; Wang, S; Zhu, S; Yuan, Y; Morse, MA; Hobeika, A; Lyerly, HK
MLA Citation
Zhou, Xinna, et al. “Adoptive immunotherapy with autologous T-cell infusions reduces opioid requirements in advanced cancer patients..” Pain, vol. 161, no. 1, Jan. 2020, pp. 127–34. Pubmed, doi:10.1097/j.pain.0000000000001702.
URI
https://scholars.duke.edu/individual/pub1415110
PMID
31568023
Source
pubmed
Published In
Pain
Volume
161
Published Date
Start Page
127
End Page
134
DOI
10.1097/j.pain.0000000000001702