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:

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

Eisai H3B-6527-G000-101 - 1012

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

Treetop Aslan

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

Publications:

Longitudinal patterns of chemotherapy (CT) use in metastatic colorectal cancer (mCRC).

15082 Background: As mCRC survival increases beyond 2 years, patients (pts) have more exposure to multiple CT regimens. Insight into patterns of care in mCRC treatment is crucial to understanding physician and patient decision-making priorities. METHODS: Using a population-based strategy, we identified CRC cases from 1 academic and 9 community oncology practices in the southeastern US with mCRC diagnosed between 6/03-6/06, and treatment with an oxaliplatin- (O) or irinotecan- (IR) based CT regimen during that period. Demographic, disease, treatment, and toxicity data were abstracted by retrospective chart review, double-entered and verified for accuracy. RESULTS: Of 743 charts screened, 110 were eligible: mean age 57.9 (SD 12.2), 74% Stage IV at diagnosis, 39% male, 53% white, 26% black, and 13% ≥70 years. As part of 1st-line mCRC CT, 100% of pts received regimens containing 5-fluorouracil (5-FU), 87% (95% CI 81-93%) received O, 12% (95% CI 6-18%) received IR, and 74% (95% CI 66-82%) received bevacizumab (B). The proportions of pts receiving subsequent lines of CT were: 2nd-line 48% (n=53), 3rd-line 26% (n=29), 4th-line 14% (n=15), and 5th-line 5% (n=5). From 1st to 3rd line, the use of O and B decreased, while IR use increased (see Table ). Therapy was discontinued 29% of the time for disease progression (PD) and 19% of the time for toxicity; 27% had no reason documented. 22% (n=25/114) of O- and 34% (n=20/59) of IR-containing regimens were discontinued for PD. 19% (n=21/114) of O- and 20% (n=12/59) of IR-containing regimens were discontinued for toxicity. CONCLUSIONS: Along with 5-FU, O and B were most commonly used in 1st-line for mCRC. Use of O decreased and IR increased as treatment progressed beyond 1st-line. [Table: see text] [Table: see text].
Authors
Herndon, JE; Zafar, Y; Marcello, J; Wheeler, J; Rowe, K; Morse, MA; Abernethy, AP
MLA Citation
Herndon, J. E., et al. “Longitudinal patterns of chemotherapy (CT) use in metastatic colorectal cancer (mCRC)..” J Clin Oncol, vol. 26, no. 15_suppl, May 2008.
URI
https://scholars.duke.edu/individual/pub1161991
PMID
27950330
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
26
Published Date
Start Page
15082

Precision and linearity targets for validation of an IFNgamma ELISPOT, cytokine flow cytometry, and tetramer assay using CMV peptides.

BACKGROUND: Single-cell assays of immune function are increasingly used to monitor T cell responses in immunotherapy clinical trials. Standardization and validation of such assays are therefore important to interpretation of the clinical trial data. Here we assess the levels of intra-assay, inter-assay, and inter-operator precision, as well as linearity, of CD8+ T cell IFNgamma-based ELISPOT and cytokine flow cytometry (CFC), as well as tetramer assays. RESULTS: Precision was measured in cryopreserved PBMC with a low, medium, or high response level to a CMV pp65 peptide or peptide mixture. Intra-assay precision was assessed using 6 replicates per assay; inter-assay precision was assessed by performing 8 assays on different days; and inter-operator precision was assessed using 3 different operators working on the same day. Percent CV values ranged from 4% to 133% depending upon the assay and response level. Linearity was measured by diluting PBMC from a high responder into PBMC from a non-responder, and yielded R2 values from 0.85 to 0.99 depending upon the assay and antigen. CONCLUSION: These data provide target values for precision and linearity of single-cell assays for those wishing to validate these assays in their own laboratories. They also allow for comparison of the precision and linearity of ELISPOT, CFC, and tetramer across a range of response levels. There was a trend toward tetramer assays showing the highest precision, followed closely by CFC, and then ELISPOT; while all three assays had similar linearity. These findings are contingent upon the use of optimized protocols for each assay.
Authors
Maecker, HT; Hassler, J; Payne, JK; Summers, A; Comatas, K; Ghanayem, M; Morse, MA; Clay, TM; Lyerly, HK; Bhatia, S; Ghanekar, SA; Maino, VC; Delarosa, C; Disis, ML
MLA Citation
Maecker, Holden T., et al. “Precision and linearity targets for validation of an IFNgamma ELISPOT, cytokine flow cytometry, and tetramer assay using CMV peptides..” Bmc Immunol, vol. 9, Mar. 2008. Pubmed, doi:10.1186/1471-2172-9-9.
URI
https://scholars.duke.edu/individual/pub726641
PMID
18366814
Source
pubmed
Published In
Bmc Immunology
Volume
9
Published Date
Start Page
9
DOI
10.1186/1471-2172-9-9

Diseases of the Gallbladder and Bile Ducts: Diagnosis and Treatment: Second Edition

An interdisciplinary reference book for the diagnosis and treatment of gallbladder and bile duct diseases. With recent developments in the management of hepatobiliary diseases including liver transplantation, this new edition aids all members of the team by addressing both the biliary indications for and biliary complications of these procedures. It's divided into three sections on anatomy, pathophysiology, and epidemiology; diagnostic and therapeutic approaches including the latest therapeutic modalities; and specific conditions. Includes more than 250 illustrations for rapid reference. Each chapter now has a Q and A section and begins with a list of objectives outlining the chapter's goals. In addition, a number of new imaging modalities are presented in this new edition. It takes an integrated medical, surgical and radiological approach, making this invaluable to all members of the team who deal with complications of liver transplantation and the management of patients. © 2006 by Blackwell Publishing Ltd.
Authors
Clavien, PA; Baillie, J; Morse, MA; Selzner, M
MLA Citation
Clavien, P. A., et al. “Diseases of the Gallbladder and Bile Ducts: Diagnosis and Treatment: Second Edition.” Diseases of the Gallbladder and Bile Ducts: Diagnosis and Treatment: Second Edition, Oct. 2007, pp. 1–428. Scopus, doi:10.1002/9780470986981.
URI
https://scholars.duke.edu/individual/pub1004195
Source
scopus
Published In
Diseases of the Gallbladder and Bile Ducts: Diagnosis and Treatment: Second Edition
Published Date
Start Page
1
End Page
428
DOI
10.1002/9780470986981

Resection of noncolorectal nonneuroendocrine liver metastases: a comparative analysis.

BACKGROUND: Although established for metastatic colorectal (CR) and neuroendocrine (NE) malignancies, the role of partial hepatectomy in management of metastases from other primaries (NCRNE) is not well-defined. STUDY DESIGN: The objective of this retrospective study is to compare outcomes after partial hepatectomy for NCRNE, NE, and CR metastases and to identify factors associated with longterm survival for patients with NCRNE diseases. Tumor characteristics, treatments, and outcomes of 360 consecutive patients undergoing resection of NCRNE (n = 82), CR (n = 245), and NE (n = 33) hepatic metastases from 1995 to 2005 were analyzed. NCRNE tumors included breast (n = 20), sarcomas (n = 19), genitourinary (n = 18), melanoma (n = 11), and other (n = 14) cancers. The start date for follow-up and survival analyses was the date of partial hepatectomy. RESULTS: For patients with NCRNE, CR, and NE tumors, there were no marked differences in postoperative mortality (4%, 4%, and 9%) or complication (30%, 42%, and 42%) rates. Median overall survival was longest for NE patients (not yet reached) versus NCRNE and CR (both 44 months) patients (p < 0.05, log-rank test). NCRNE patients had shorter disease-free survival than CR counterparts (13 versus 16 months), p < 0.05 (log-rank test). After median followup of 59 months for NCRNE patients, actuarial 5-year overall and disease-free survival was 37% and 16%, respectively, with 15 5-year survivors. Multivariable analysis suggests that interval from discovery of liver metastases to resection > 6 months (p = 0.08) and administration of chemoradiotherapy after resection (p = 0.06) might be associated with improved overall survival. CONCLUSIONS: In selected patients, resection of NCRNE liver metastases can be done safely with survival similar to CR metastases. Delay of liver resection for at least 6 months and treatment with chemoradiotherapy after resection might be associated with improved longterm survival after partial hepatectomy.
Authors
Reddy, SK; Barbas, AS; Marroquin, CE; Morse, MA; Kuo, PC; Clary, BM
MLA Citation
Reddy, Srinevas K., et al. “Resection of noncolorectal nonneuroendocrine liver metastases: a comparative analysis..” J Am Coll Surg, vol. 204, no. 3, Mar. 2007, pp. 372–82. Pubmed, doi:10.1016/j.jamcollsurg.2006.12.019.
URI
https://scholars.duke.edu/individual/pub726578
PMID
17324770
Source
pubmed
Published In
Journal of the American College of Surgeons
Volume
204
Published Date
Start Page
372
End Page
382
DOI
10.1016/j.jamcollsurg.2006.12.019

Investigation of HIFU-induced anti-tumor immunity in a murine tumor model

To determine whether HIFU treatment can elicit a systemic, anti-tumor immune response in vivo, MC-38 solid tumors grown subcutaneously at the right hindlimbs of C57BL/6 mice were treated in an experimental HIFU system. Three different treatment strategies that produce thermal, mechanical, or thermal combined with mechanical damage to the tumor tissue were evaluated. To detect anti-tumor immune response, a tumor challenge was performed on the left hindlimbs of the mice one day following the HIFU treatment, and subsequently, cytotoxic T lymphocyte (CTL) response was evaluated on day 14. All three HIFU treatment strategies were found to cause significant regression of the primary tumor, with the best suppressive effect produced by the thermal HIFU. In contrast, the most significant regression of the challenged tumor with concomitantly elevated CTL response were detected in mice treated by the mechanical HIFU, followed by the thermal combined with mechanical HIFU, but not in mice treated by the thermal HIFU alone. These findings suggest that alternative treatment strategies that promote mechanical lysis of the tumor cells (in contrast to purely thermal ablation) may enhance HIFU-induced anti-tumor immune response. © 2006 American Institute of Physics.
Authors
Hu, Z; Yang, XY; Liu, Y; Morse, MA; Lyerly, HK; Clay, TM; Zhong, P
MLA Citation
Hu, Z., et al. “Investigation of HIFU-induced anti-tumor immunity in a murine tumor model.” Aip Conference Proceedings, vol. 829, May 2006, pp. 241–45. Scopus, doi:10.1063/1.2205474.
URI
https://scholars.duke.edu/individual/pub785637
Source
scopus
Published In
Aip Conference Proceedings
Volume
829
Published Date
Start Page
241
End Page
245
DOI
10.1063/1.2205474