Immunotherapy research programs across Geisel have been at the forefront of efforts to mobilize the immune system to fight disease and to build the molecular platforms that have been essential to the success of new therapies. Today, our faculty are pioneering the identification of new immune system targets, creating and testing new ways of activating the immune system, and pursuing strategies to induce long-term immunity to life-threatening diseases. New philanthropic support will fuel discovery and clinical translation within one of Geisel’s most successful and high-potential areas of innovation.
Scientists are engineering immune cells to find and kill tumor cells. Geisel immunologist Charles Sentman, PhD, and colleagues from across Dartmouth are developing CAR T-cell therapies that can potentially treat nearly 80-90% of human tumors, as explained in this video. Read more about Dartmouth’s CAR T-cells.
Immunotherapy Innovation and Entrepreneurship at Dartmouth
Three biotech companies founded by immunologists at Geisel and Norris Cotton Cancer Center have translated groundbreaking scientific discoveries made at Dartmouth into remarkable treatments for patients.
“Medarex survived in the early days because our clinical colleagues made time to work with us and lead clinical trials with Medarex antibodies, right here, at Dartmouth.”
—Paul Guyre, PhD, Medarex Co-Founder
Medarex (est. 1987)
INNOVATION: At a time when most of biotech shied away from cancer immunotherapy, Medarex invested in two promising antibodies—anti-CTLA-4 and anti-PD-1—designed to essentially take the brakes off immune cells so they can attack tumors.
IMPACT: The therapies became the blockbuster, life-saving cancer drugs ipilimumab (Yervoy) and nivolumab (Opdivo) and led to the 2018 Nobel Prize in Physiology and Medicine being awarded to the scientists who brought anti-CTLA-4 and anti-PD-1 to Medarex.
Bristol-Myers Squibb purchased Medarex in 2009 for $2.4 billion; a portion of those profits fund translational research at Geisel.
Medarex and Early Immunotherapies Timeline
1999 - Medarex acquires the rights to two antibodies—anti-CTLA-4 and anti-PD-1—and later develops them into two of the top immunotherapies in use today: ipilimumab (Yervoy) and nivolumab (Opdivo). Most pharmaceutical companies considered immunotherapy too risky at that time.
2009 - Bristol-Myers Squibb purchases Medarex for $2.4 billion. A portion of the profits support the annual Munck-Pfefferkorn Awards, which fund new biomedical research projects at the Geisel School of Medicine that have high potential to benefit patients and to generate future revenue through grants or entrepreneurial endeavors.
2011 - The Food and Drug Administration approves ipilimumab (Yervoy) for late-stage melanoma. The approved uses of Yervoy expand over subsequent years.
2013 - Science names cancer immunotherapy the “breakthrough of the year,” noting results from several recent clinical trials and declaring immunotherapy a “turning point in cancer.”
2014 - The Food and Drug Administration approves nivolumab (Opdivo) for advanced melanoma. The approved uses of Opdivo expand over subsequent years, including combination treatment with Yervoy and Opdivo for certain cancers.
2018 - Nobel Prize in Physiology and Medicine is awarded to two scientists who brought anti-CTLA-4 and anti-PD-1 technology to Medarex—the antibodies that became Yervoy and Opdivo.
Celdara (est. 2008)
INNOVATION: Celdara partnered with Dartmouth immunologist Charles Sentman, PhD, who created a unique form of CAR T-cells based on a natural receptor. Unlike other CAR T-cells on the market, these engineered immune cells can target up to 80%-90% of human cancers and can be allogeneic—compatible with any patient.
IMPACT: Celdara and Sentman’s CAR T-cells—now in clinical trials in the U.S. and Europe against seven types of cancer—will revolutionize CAR T-cell therapy, making it widely effective, efficient, and affordable.
Celdara and Natural Receptor CAR T-cells Timeline
2008 - Dartmouth immunologist Mike Fanger, PhD, and Jake Reder, PhD, director of the New Ventures Office at Dartmouth’s medical school, found Celdara Medical, a company dedicated to helping investigators secure the funding and partners needed to translate biomedical discoveries into medicines. (Another Dartmouth immunologist and Medarex co-founder, Paul Guyre, PhD, later joins Celdara as vice president for research and discovery.)
2009 - Charles Sentman, PhD, develops the design and use of TCR-defective T-cells as the basis for allogeneic CAR T-cell therapy. This approach turns a gene therapy process into a cell product that could be made available to any patient.
2015 - Celdara partners with Celyad to run Phase I clinical trials testing the safety, feasibility, and dosing of CAR T-cell therapies based on research by Dartmouth immunologist Charles Sentman, PhD, and his lab.
2018 - The NKG2D CAR (CYAD-01) is in multiple ongoing Phase I/II clinical testing against seven types of cancer. The allogeneic NKG2D CAR (CYAD-101) enters Phase I clinical testing.
ImmuNext (est. 2010)
INNOVATION: Known as immune checkpoint inhibitors, the ImmuNext therapies target immune system proteins VISTA and CD154—both of which regulate immune cells and play important roles in cancer and a range of autoimmune diseases, such as lupus and multiple sclerosis.
IMPACT: Both therapies have been licensed to large pharmaceutical companies and are in multicenter, Phase I clinical trials in cancer and autoimmunity. Early results are promising.
ImmuNext and Immune Checkpoints Inhibitors Timeline
2010 - The Noelle lab discovers a new immune system protein, called VISTA, which functions as a negative checkpoint regulator, preventing immune cells from attacking tumors.
Noelle founds ImmuNext, embedded within Norris Cotton Cancer Center, to develop therapies to block VISTA and to target CD154-CD40 interactions, thereby enhancing the body’s own immune responses to cancer.
2012 - ImmuNext teams up with Janssen Biotech, a Johnson & Johnson subsidiary, to develop anti-VISTA therapies and subsequent clinical trials.
2016 - ImmuNext grants Roche a worldwide, exclusive license to develop and commercialize therapeutics that target the VISTA immune system pathway.
2017 - ImmuNext grants Sanofi an exclusive, worldwide license to develop and commercialize INX-021, a CD40L monoclonal antibody. Preclinical studies indicate a high potential for the medication to treat a range of autoimmune diseases, including lupus and multiple sclerosis.