Cancer won't have a single solution, so Ludwig's dedication to life-changing science takes many forms. In individual laboratories or as international teams, our scientists are working the problem from every angle, seeking to unravel the basic biological underpinnings of cancers. At Ludwig, discovery is just the beginning of the journey to improved human health.
Ludwig brings together multidisciplinary teams of investigators to tackle the biggest issues in cancer research with resources beyond those available to any single laboratory. From basic research to clinical trials, we find the best minds to make discoveries and develop new ways to prevent and control cancer. Robert Strausberg leads Ludwig's continuing effort to spot opportunities and facilitate scientific synergies.
The skin cancer melanoma has long been the focus of groundbreaking research at Ludwig, and we are poised to make substantial advances against this common and frequently aggressive cancer. Our longstanding goal has been to enhance the power of the immune system to recognize and eliminate these cancers in people. Through long-term and innovative approaches, Ludwig scientists in New York and Brussels found that melanomas produce specific proteins that are quite rare in normal cells outside the reproductive system. When tumors produce these and other antigens, the cancer cells can be recognized by our immune system and a powerful natural response often results in early elimination of potential cancers. In some cases, however, the cancers escape—in part because the cells have developed active mechanisms to thwart the immune response—resulting in aggressive disease.
To drive the balance in favor of the immune system, Ludwig is attempting to enhance the natural response while reducing the ability of cancer cells to fight back. Ludwig has long played a role in this research, and we’re making progress toward improved patient outcomes. This work also builds on the recent international effort, including Ludwig, to comprehensively identify the genomic mutations that underlie the initial formation of melanomas. Our researchers are now attempting to combine immunological approaches with the development of small molecules that target prominent genomic alterations to defeat the formation and progression of deadly melanomas.
Cancer immunotherapy is a treatment designed to stimulate the ability of the immune system to attack tumor cells. Ludwig researchers have made major contributions in this area, both through basic discoveries and the development and testing of new therapies.
Long-term, fundamental research by Ludwig scientists in Brussels and New York resulted in the discovery of a large group of molecular antigens, including MAGE and NY-ESO-1, that could be incorporated into therapies to boost the immune response to melanoma and many other forms of cancer. In clinical trials conducted by Ludwig scientists and their colleagues in Melbourne and Lausanne, these antigens induced significant levels of anti-tumor immunity in vaccinated patients. The clinical efficacy of several cancer immunotherapies incorporating these antigens is being evaluated by some of Ludwig’s commercial partners, including two large late-stage studies in melanoma and lung cancer.
Natural immunity is regulated by several interdependent mechanisms that maintain a balance between effective responses to pathogenic assault and excessive responses resulting in autoimmunity. These checkpoints might inadvertently protect tumors from the full force of natural anti-tumor responses. Using blocking monoclonal antibodies to target an immune checkpoint called CTLA-4, Ludwig researchers in New York achieved durable responses in advanced melanoma patients that helped lead to the approval of the first new treatment for advanced melanoma in many years. Several new Ludwig clinical trials are underway in New York and Melbourne, evaluating novel combinations of the anti-CTLA-4 therapy with other agents. Building on that work, Ludwig scientists are testing new antibodies targeting other immune checkpoints, in combinations with other antibodies or in combinations with treatments such as radiotherapy.
In addition to blocking checkpoints, other monoclonal antibodies can stimulate anti-tumor immunity or be used to deliver toxins directly to tumor cells. Ludwig researchers in New York and Melbourne have discovered, characterized and clinically tested several anti-cancer monoclonal antibodies targeting diverse tumor and stromal cell antigens. Many of these antibodies are being developed as new anti-cancer drugs by our commercial partners, including several Ludwig start-up companies.
Ludwig scientists in Brussels revealed another immunotherapy approach through their discovery of the immune-modulating enzymes IDO and TDO. An effort to build on this discovery by developing small-molecule drugs to treat tumors is being investigated by Ludwig scientists in Brussels and San Diego, in collaboration with a Ludwig start-up company established to develop this technology.
Ludwig basic and clinical scientists, together with our team of clinical trial design and management experts, continually collaborate with the international research community to design and evaluate new combinations of immunotherapies. Much of this work is conducted in partnership with the Cancer Research Institute and through our joint CVC Trials Network.
Colon cancer, one of the most common solid cancers, can become very aggressive and deadly. Cancer survival rates have improved substantially, though, mainly because of advances in early detection such as colonoscopy. Late stage cancers remain difficult to treat and too often are fatal.
One of the distinct features of colon cancer is that early stage pre-cancerous growth can be detected and studied though direct examination and biopsy of tissue samples. As cells progress toward cancer the polyps grow and change, ultimately becoming invasive and metastasizing to different regions of the body. The team of scientists at the Ludwig Center at Johns Hopkins has conducted direct genomic analysis of different grades of polyps and has unraveled many of the specific alterations that drive colon cancer development. Fortunately, colon cancer progresses slowly, providing ample opportunity to detect and remove pre-cancerous polyps.
The Ludwig Colon Cancer Initiative is focused on several critical pursuits that ultimately could benefit patients. First, our team in Baltimore is developing blood tests that could be performed during routine physical exams that we expect will ultimately detect early stages of colon cancer. We also are testing the applicability of this approach to the routine monitoring of cancer patients as a potential way to predict recurrences after initial treatments such as surgery and chemotherapy. In addition, we are studying about 1,000 samples collected by the Ludwig team in Melbourne to identify the potential influences of specific genomic changes on the course of this disease, and apply that knowledge to improving the treatment of late-stage colon cancers.
Researchers around the world are learning more every day about the environmental factors that can trigger cancer. Some of these factors, such as cigarette smoking or too much exposure to the sun’s ultraviolet light, are major factors in the development of lung or melanoma, respectively. Nutritional factors are closely associated with colon cancer.
Reducing exposure to these factors—quitting smoking, for example—can diminish the chances of developing cancer. Another way to reduce risk is through the identification of certain viruses that can cause cancer—as we now understand the relationship of human papilloma virus and cervical cancer. For this cancer, early detection has translated to better patient outcome. Most important, an international team, with key leadership from Ludwig scientists in Brazil, performed research and clinical studies that led to the vaccine Gardasil, now available to prevent HPV infection and the cervical cancer associated with that virus.
For some tumor types, we can detect cancer cells at very early stages of their progression toward disease. Although more research is needed, we know that cancers detected early are more treatable. Indeed, as cancer treatment methods improve, early detection will increasingly lead to better long-term outcomes and better quality of life for cancer patients.
At Ludwig, we are committed to developing early detection and intervention methods so cancers are eliminated before they become life-threatening. For example, to develop better ways to detect cancers early, Ludwig is working with the Conrad N. Hilton Foundation on methods that ideally could be performed during routine physical exams. In this collaborative program, a team of Ludwig scientists in Baltimore, Melbourne and San Diego is developing new technologies and strategies such as a blood test that could detect DNA that has been shed from tumors and might indicate an emerging disease. Ultimately, we envision blood tests (or other minimally invasive techniques) that could be performed as part of a patient’s annual physical exam to recognize emerging cancers, just as blood tests today can identify indicators of potential cardiovascular disease. In keeping with this model, our team also is working on the development and identification of potential drugs that could prevent the progression of pre-cancers to cancer.
In ongoing clinical studies, Ludwig scientists are investigating whether these approaches could be used to guide interventions for patients with cancer. We envision that this approach will help prevent recurrence of cancers after initial treatment.
Ludwig researchers have made substantial contributions to the emerging view that breast cancer comprises a multitude of diseases, each presenting different opportunities for intervention through small-molecule drugs or immunotherapy, among other strategies.
Ludwig scientists in the United States, Europe, South America and Australia are using the most advanced DNA sequencing technologies to discover genomic alterations that contribute to the development of breast cancers. Our research focuses on some of the most challenging aspects of breast cancers, such as uncovering the specific molecular mechanisms of metastasis—the process by which cancer cells migrate from the breast to other parts of the body.
Our scientists also are working to develop new interventions for a particularly difficult-to-treat breast cancer referred to as triple-negative. These cancers do not express estrogen and progesterone receptors, as well as HER2/neu, which are important targets for breast cancer intervention. Therefore, many treatments that might normally be used are not effective. For this cancer, Ludwig scientists seek to identify new targets—especially those that might be susceptible to immunotherapy—that could lead to more effective interventions.
Brain cancers can afflict people of any age. Some are highly aggressive and deadly while others are more benign. Ludwig continues to make major contributions to the understanding of brain cancers through the combined efforts of researchers in the United States, Europe and Australia.
Based on the discovery of an altered form of a key receptor, EGFR, on the cell surface of a most deadly brain cancer, glioblastoma multiforme (GBM), Ludwig scientists developed antibodies that target this receptor only in GBMs and not in normal cells. This ongoing effort is now at the clinical stage, illustrating Ludwig’s long-term scientific commitment to win the fight against aggressive cancers such as GBM.
Our team in Baltimore sequenced the complete set of human genes to identify those that contribute to the development and progression brain cancers. We now know many of the genetic changes that combine to generate brain cancers such as GBM, as well as a childhood brain cancer called medulloblastoma. With this information our scientists seek to build upon their EGFR targeting work through combination strategies intended to stop a patient’s cancer from growing and prevent it from coming back. In this effort, Ludwig teams—basic and clinical scientists, medicinal chemists, structural scientists and experts in clinical trial design and management—work with international partners to develop new interventions based on immunotherapy, as well as small-molecule drugs.