Program Activities and Selected Scientific Reports
The Cancer Immunotherapy Program at Norris Cotton Cancer Center is located at Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire. Charles Sentman, PhD and Kenneth R. Meehan, MD are the leaders of this program, which is one of six foundational research programs at the Norris Cotton Cancer Center. The twenty-one members of Cancer Immunotherapy come from seven departments at Geisel School of Medicine and Thayer School of Engineering at Dartmouth College.
The program's members meet monthly to exchange ideas and research updates. A focus group on Melanoma Immunotherapy provides another venue for scientific discussion and is organized by Cancer Immunotherapy. On an annual basis, Cancer Immunotherapy gathers for a retreat specific to immunology. As appropriate, program members plan topical meetings to address particular issues in great depth. A recent example is the program planned by Randy Noelle, PhD dedicated to the development of a new immune checkpoint inhibitor called VISTA.
The lively Dartmouth campus provides many other opportunities for scientific involvement and members from Cancer Immunotherapy are regular participants in both the Microbiology & Immunology, and Immunology Seminar Series. Similarly, symposia are organized, such as the May 2014 Dartmouth Immunology & Immunotherapy Symposium.
As a program, Cancer Immunotherapy organizes and promotes new funding opportunities for members, such as Charles Sentman's NCI funded project with Mary Jo Turk, PhD, Marc Ernstoff, MD, Randy Noelle, PhD, and David Mullins, PhD, entitled “A Novel NKG2D-Specific BiTE Cancer Immunotherapy”. This program is aimed to develop a novel immunotherapy approach for melanoma and lymphoma based on specific targeting of immune cells against tumor cells. They also participate in themed faculty recruitment to strengthen the program's ability to address its themes. William Green, PhD's participation in the tumor immunology search that resulted in the strategic hire of David Mullins is a prime example.
Education and mentoring are priorities of Cancer Immunotherapy. David Mullins is active teaching immunology in the microbiology course for first year medical students at Geisel School of Medicine at Dartmouth. Mary Jo Turk also teaches immunology in an upper level course for Dartmouth undergraduates. Jim Gorham, MD, PhD is the associate director for education at NCCC. Throughout the program, there is active mentoring of junior faculty. Two particularly successful mentor-mentee relationships are Randy Noelle and Lily Wang, PhD, and Edward Usherwood, PhD with Yina Huang, PhD.
At the national level, Cancer Immunotherapy members are involved in boards, study sections, and scientific events. For example, Charles Sentman serves on the TME (tumor microenvironment) study section at the NIH, and Marc Ernstoff serves on the national advisory board for CITN.
2013 Selected Scientific Progress & Achievements
Dr. Ernstoff’ s current work focuses on the role of driver mutations, inhibiting these pathways in melanoma in host responses, and determining how these reactions may be exploited to enhance immune response to cancer for therapeutic purposes (Exp Hematol Oncol, 2013).
Dr. Sentman and colleagues have published previously on a new therapeutic protein, scFv-NKG2D, a bispecific T cell engager used to target immune cells against tumors and immunosuppressive cells. Some of these intriguing findings were investigated further by Dr. Meehan, in conjunction with Drs. Sentman and Ernstoff, in a clinical trial examining NKG2D cell recovery following an autologous stem cell transplant. Dr. Meehan’s translational research has focused on the immune reconstitution of CD3+CD8+ cells bearing the NKG32D receptor in patients following transplantation (Transfusion, In Press). A series of Phase I and II clinical trials has been completed, treating 55 patients with myeloma receiving a stem cell transplant, for which Dr. Meehan received an IND. These Phase I and Phase II clinical trials employed immunotherapy, with or without adoptive cellular therapy with activated autologous T cells, after hematopoietic stem cell transplantation in myeloma patients. These T cells recognized tumor cells through the NKG2D receptor on CD3+ T cells (Biol Blood Marrow Transplant 2013).
NCCC continues as a member of the NCI-sponsored Cancer Immunotherapy Trials Network (CITN). Drs. Ernstoff and Meehan are the site Co-PIs. This selection provides NCCC with access to new therapies, enabling NCCC involvement in multi-center cancer immunotherapy trials Drs. Griswold, Sentman, and Turk are part of an ongoing collaboration with Dartmouth’s Thayer School of Engineering and the NCCC Center for Cancer Nanotechnology Excellence (CCNE) to study targeted magnetic nanoparticle-mediated hyperthermia of solid tumors. This work is supported by Dartmouth’s inclusion in the NCI-funded national Alliance for Cancer Nanotechnology (U54).
2012 Selected Scientific Accomplishments
- Dr. Marc Ernstoff helped to lead a study on the use of ipilimumab in melanoma and brain metastasis. The aim was to investigate the safety and activity of this drug, specifically in patients with brain metastases. Patients with melanoma and brain metastases from ten US centers, who were older than 16 years, were entered into two parallel cohorts. The interpretation of this study was that ipilimumab has activity in some patients with advanced melanoma and brain metastases, particularly when metastases are small and asymptomatic. The drug had no unexpected toxic effects in this population (Margolin, 2012)
- Margolin K, Ernstoff MS, Hamid O, Lawrence D, McDermott D, Puzanov I, Wolchok JD, Clark JI, Sznol M, Logan TF, Richards J, Michener T, Balogh A, Heller KN, Hodi FS (2012). Ipilimumab in patients with melanoma and brain metastases: An open-label, Phase 2 trial. Lancet Oncol 13(5):459-465.
- Dr. Richard Barth and colleagues have published a clinical study on the effects of neo-adjuvant therapy in pancreatic ductal adenocarcinoma (PDAC]. They investigated cetuximab, with twice-weekly gemcitabine and intensity-modulated radiotherapy (IMRT), as neo-adjuvant therapy in patients with localized or locally advanced PDAC. The therapy was tolerable and active in PDAC, with 61% of patients having stable disease and 30% having a partial response by RECIST criteria (Pipas, 2012)
- Pipas JM, Zaki BI, McGowan MM, Tsapakos MJ, Ripple GH, Suriawinata AA, Tsongalis GJ, Colacchio TA, Gordon SR, Sutton JE, Srivastava A, Smith KD, Gardner TB, Korc M, Davis TH, Preis M, Tarczewski SM, Mackenzie TA, Barth RJ, Jr. (2012, In press). Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma. Ann Oncol. PMC Journal - In Process