Michael Morse

Overview:

We are studying the use of immune therapies to treat various cancers, including gastrointestinal, breast, and lung cancers and melanoma. These therapies include vaccines based on dendritic cells developed in our laboratory as well as vaccines based on peptides, viral vectors, and DNA plasmids. Our group is also a national leader in the development and use of laboratory assays for demonstrating immunologic responses to cancer vaccines. Finally, we are developing immunotherapies based on adoptive transfer of tumor and viral antigen-specific T cells.

Our current clinical trials include phase I and II studies of immunotherapy for: patients with metastatic malignancies expressing CEA, pancreatic cancer, colorectal cancer, breast cancer, and ovarian cancer, and leukemias following HSCT. My clinical area of expertise is in gastrointestinal oncology, in particular, the treatment of hepatic malignancies, and malignant melanoma.

Key words: dendritic cells, immunotherapy, vaccines, T cells, gastrointestinal oncology, melanoma, hepatoma

Positions:

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Professor in the Department of Surgery

Surgery, Surgical Sciences
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1990

Yale University

Medical Resident, Medicine

University of Washington

Fellow in Hematology-Oncology, Medicine

Duke University

Grants:

Characterization of Tumor Immunobiological Factors that Promote Lymphovascular Invasion and Dissemination in Locally Advanced Breast Cancer

Administered By
Surgery, Surgical Sciences
Awarded By
Department of Defense
Role
Co Investigator
Start Date
End Date

Cancer Care Quality Measures: Diagnosis and Treatment of Colorectal Cancer

Administered By
Institutes and Centers
Awarded By
Agency for Healthcare Research and Quality
Role
Investigator
Start Date
End Date

SPICE-ColoAd1-1003

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

HIMALAYA

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

HALO-110-101

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

Publications:

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

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

Reporting Long Term Survival Following Precision Tumor-Targeted Gene Delivery to Advanced Chemotherapy-Resistant Malignancies: An Academic Milestone

Authors
Liu, SY; Chawla, SP; Bruckner, H; Morse, MA; Federman, N; Ignacio, JG; San Juan, F; Manalo, RA; Hall, FL; Gordon, EM
MLA Citation
URI
https://scholars.duke.edu/individual/pub1381850
Source
wos
Published In
Molecular Therapy
Volume
27
Published Date
Start Page
133
End Page
133

A phase Ib study of capecitabine and ziv-aflibercept followed by a phase II single-arm expansion cohort in chemotherapy refractory metastatic colorectal cancer.

BACKGROUND: Patients with chemotherapy refractory metastatic colorectal cancer (CRC) have a poor prognosis and limited therapeutic options. In this phase Ib/II clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RPTD) for the combination of capecitabine and ziv-aflibercept, and then we evaluated the efficacy of the combination in patients with chemotherapy refractory metastatic CRC. METHODS: All patients were required to have a Karnofsky Performance Status > 70% and adequate organ function. The phase Ib dose escalation cohort included patients with advanced solid tumors who had progressed on all standard therapies. Using a standard 3 + 3 design, we identified the MTD and RPTD for the combination. Fifty patients with metastatic CRC who had progressed on or were intolerant of a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab were then enrolled in a single-arm phase II expansion cohort, and were treated at the RPTD. Prior EGFR antibody therapy was required for subjects with RAS wildtype tumors. The primary endpoint for the expansion cohort was progression-free survival (PFS) at two months. Secondary endpoints included objective response rate (ORR) and overall survival (OS). RESULTS: A total of 63 patients were enrolled and evaluable for toxicity (13 dose escalation; 50 expansion). The MTD and RPTD were: capecitabine 850 mg/m2, P.O. bid, days 1-14, and ziv-aflibercept 6 mg/kg I.V., day 1, of each 21-day cycle. In the expansion cohort, 72% of patients were progression-free at two months (95% confidence interval [CI], 60-84%). Median PFS and OS were 3.9 months (95% CI, 2.3-4.5) and 7.1 months (95% CI: 5.8-10.0), respectively. Among all patients evaluable for toxicity, the most common treatment related adverse events (all grade [%]; grade ≥ 3 [%]) included palmar-plantar erythrodysesthesia (41%; 6%), hypertension (33%; 22%), and mucositis (19%; 5%). RNA was isolated from archived tumor specimens and gene expression analyses revealed no association between angiogenic biomarkers and clinical outcomes. CONCLUSION: The combination of capecitabine and ziv-aflibercept at the RPTD demonstrated acceptable safety and tolerability. PFS at 2 months in patients with chemotherapy refractory metastatic CRC was significantly greater than that in historical controls, indicating that this combination warrants further study. TRIAL REGISTRATION: This clinical trial was registered in the www.clinicaltrials.gov system as NCT01661972 on July 31, 2012.
Authors
Strickler, JH; Rushing, CN; Niedzwiecki, D; McLeod, A; Altomare, I; Uronis, HE; Hsu, SD; Zafar, SY; Morse, MA; Chang, DZ; Wells, JL; Blackwell, KL; Marcom, PK; Arrowood, C; Bolch, E; Haley, S; Rangwala, FA; Hatch, AJ; Nixon, AB; Hurwitz, HI
MLA Citation
Strickler, John H., et al. “A phase Ib study of capecitabine and ziv-aflibercept followed by a phase II single-arm expansion cohort in chemotherapy refractory metastatic colorectal cancer..” Bmc Cancer, vol. 19, no. 1, Nov. 2019. Pubmed, doi:10.1186/s12885-019-6234-8.
URI
https://scholars.duke.edu/individual/pub1417915
PMID
31675952
Source
pubmed
Published In
Bmc Cancer
Volume
19
Published Date
Start Page
1032
DOI
10.1186/s12885-019-6234-8