Program Activities and Selected Scientific Reports
The Immunology and Immunotherapy Research Program continues to focus on bringing basic scientists and clinicians together to address issues of cancer immunotherapy. Members are involved in:
- Expand our efforts in understanding the natural and induced immune responses to cancer.
- Develop the use of CD40/TLR agonists as a cancer vaccine platform in melanoma.
- Develop T cell-based therapies for the treatment of cancer.
- Continue to build basic and clinical interest in the treatment of ovarian cancer.
- Identify critical areas in cancer immunotherapy for faculty recruitment to grow and strengthen existing programs.
- Execute and expand efforts in DC-based vaccine trials
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