Ludwig Cancer Research

Last updated
Ludwig Cancer Research
Founded1971
Founder Daniel K. Ludwig
Focus Cancer Research
Headquarters New York, NY, USA
Zürich, Switzerland (European Office)
Area served
International
Key people
Edward A. McDermott,Jr., President and CEO, Chi Van Dang, MD,PhD, Scientific Director
Website www.ludwigcancerresearch.org

Ludwig Cancer Research is an international community of scientists focused on cancer research, with the goal of preventing and controlling cancer. [1] It encompasses the Ludwig Institute for Cancer Research, an international non-profit organization founded in 1971 by philanthropist Daniel K. Ludwig. The Institute is headquartered in New York City, with a European office located in Zürich. There are currently three Ludwig Branches: Ludwig Lausanne, Ludwig Oxford and Ludwig Princeton. In addition, there are six Ludwig Centers at leading institutions across the United States of America. Together, the Institute, Branches and Centers are known as Ludwig Cancer Research.

Contents

Since its founding in 1971, Ludwig Cancer Research has committed more than US$2.5 billion to cancer research. Ludwig Cancer Research focuses on both basic research and translational research, with specific emphasis on cell biology, genomics, immunology, neuroscience, prevention, cell signaling, stem cells, therapeutics, and tumor biology, as well as clinical trials and the design and development of small molecules with drug-like properties. [2] Its researchers also focus on particular types of malignancy, including brain cancer, breast cancer, colon cancer, and melanoma. [3]

Founder and history

Daniel K. Ludwig was a shipping magnate and real estate investor. Born in South Haven, Michigan in 1897, he used a $5,000 loan from his father to create a global business based on a fleet of supertankers. [4] In the 1960s and 1970s, Ludwig was among the richest men in the world, owning approximately 200 companies. [5]

He founded the Ludwig Institute for Cancer Research as an independent organization in 1971, the same year that the “War on Cancer,” declared by his friend President Richard Nixon, led to the establishment of the US National Cancer Institute. [6] Ludwig believed that tackling the problem of cancer required the best minds operating in the most favorable conditions with the best resources to accomplish the task. This principle continues to guide Ludwig Cancer Research. [7]

Daniel K. Ludwig endowed the Institute with all of the foreign assets from his business holdings. Upon his death in 1992, that endowment had grown to more than $700 million, [4] and, as of 2012, it stands at more than $1.2 billion. [6]

After Ludwig's death, his US-based assets were also put into a trust to support additional cancer research efforts. These funds led to the establishment of Ludwig Centers at six research institutions in 2006. [8] The Ludwig Institute for Cancer Research and Ludwig Centers have been known collectively as Ludwig Cancer Research since 2012. [9] In total, Ludwig Cancer Research has committed more than US$2.5 billion to cancer research worldwide since 1971. [10]

Mission and goals

The primary objectives of Ludwig Cancer Research are to prevent and control cancer through basic and translational research. [1]

Research

Immunotherapy

Lloyd J. Old, the organization's former director, and scientific chairman, participated in the discovery of Tumor Necrosis Factor (TNF) [11] and the tumor suppressor p53. [12] He contributed to the immunosurveillance hypothesis, from which modern cancer immunotherapy can be derived. [7]

Thierry Boon, former director of the organization's Brussels branch, made foundational contributions to the field of cancer immunotherapy. The prevailing model of carcinogenesis in the late 1970s held that spontaneously arising tumors were unlikely to elicit immune responses. Boon and his team, who believed otherwise, were the first to isolate genes that code for a family of tumor antigens and show that T cells could recognize and target cancer cells bearing such antigens. [13] This theory is being tested in a number of current clinical trials. [14]

Ludwig researchers in Melbourne discovered and cloned [15] the granulocyte-monocyte colony-stimulating factor (GM-CSF) through a collaboration with Australian immunologist Donald Metcalf. The factor is essential to the maturation of key white blood cells, and has been used extensively over the past few decades to help rebuild the immune system of patients undergoing chemotherapy. It is also being tested as a therapeutic agent in combination with several experimental immunotherapies for cancer. The Oncology Drug Advisory Committee of the US FDA recently recommended approval for T-VEC, a viral therapy for melanoma manufactured by Amgen that incorporates the gene for GM-CSF to support anti-cancer immune responses. [16]

Ludwig researchers in São Paulo played a role in establishing that human papillomavirus (HPV) infection causes cervical cancer. They ran the largest epidemiological studies of HPV infection and reported that chronic, though not transient, infection by the virus dramatically increases the risk of cervical cancer, laying the groundwork for the clinical development of an HPV vaccine. [17]

Current and former Ludwig researchers contributed to an emerging class of cancer immunotherapies known as checkpoint inhibitors. They explored the underlying immunology of the response and played a role in evaluating the first such drug in clinical trials for the treatment of advanced melanoma. [18] This led the development of new criteria for evaluating responses of cancer patients to immunotherapy in clinical trials. [19]

Cell signaling

Identification of signaling pathways and subsequent development of therapeutics are examples of contributions to the field of cell signaling. The PI3K family of proteins, for example, play an important role in cell signaling that feeds cancer. [20] This research resulted in the first Ludwig spin-off, Piramed Ltd., a biotech that sought to create cancer medicines based on this discovery. The pharmaceutical company Roche purchased the company. Drugs based on these discoveries are now being evaluated for the treatment of many cancers, including breast and lung cancer. [7]

Genomics

Contributions in the field of genomics include the work of Ludwig researchers at Johns Hopkins to sequence the full complement of genes expressed in many cancers, including head and neck, colon, and breast cancers, as well as glioblastoma multiforme (GBM). Ludwig researchers in San Diego significantly advanced studies of the epigenome, leading such efforts as the NIH's Roadmap Epigenomics Project. [21]

Leadership

The Ludwig Cancer Research board of directors helps oversee both the Ludwig Institute for Cancer Research and the Ludwig Fund. Although each of these entities has its own board, the boards comprise the same individuals. [22] The current chairman of the board is John L. Notter, an international financier and developer affiliated with a variety of companies, including Westlake Properties, Inc. [23]

The executive staff manages the organization's worldwide efforts. Edward A. McDermott, Jr has been with the organization since 1988 and its CEO since 2010. [24]

It was announced in December 2016 that Chi Van Dang will take over the role of Scientific Director in July 2017. [25] He will be responsible for coordinating the organization's global research efforts and activities.

Notable faculty

Notable awards received by past and present employees affiliated with Ludwig include:

Nobel Prize:

National Medal of Science (US):

Fellows of the National Academy of Sciences (US): [31]

Academy of Medical Sciences (UK): [39]

Locations

Branches and laboratories [42]

Ludwig Centers [42]

Related Research Articles

Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.

A cancer vaccine, or oncovaccine, is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology (immuno-oncology) and a growing subspecialty of oncology.

Virotherapy is a treatment using biotechnology to convert viruses into therapeutic agents by reprogramming viruses to treat diseases. There are three main branches of virotherapy: anti-cancer oncolytic viruses, viral vectors for gene therapy and viral immunotherapy. These branches use three different types of treatment methods: gene overexpression, gene knockout, and suicide gene delivery. Gene overexpression adds genetic sequences that compensate for low to zero levels of needed gene expression. Gene knockout uses RNA methods to silence or reduce expression of disease-causing genes. Suicide gene delivery introduces genetic sequences that induce an apoptotic response in cells, usually to kill cancerous growths. In a slightly different context, virotherapy can also refer more broadly to the use of viruses to treat certain medical conditions by killing pathogens.

Advaxis Inc. is an American company devoted to the discovery, development and commercialization of immunotherapies based on a technology platform which uses engineered Listeria monocytogenes. The company is headquartered in Princeton, New Jersey and was incorporated in Delaware in 2006.

<span class="mw-page-title-main">Steven Rosenberg</span> American cancer researcher

Steven A. Rosenberg is an American cancer researcher and surgeon, chief of Surgery at the National Cancer Institute in Bethesda, Maryland and a Professor of Surgery at the Uniformed Services University of Health Sciences and the George Washington University School of Medicine and Health Sciences. He pioneered the development of immunotherapy that has resulted in the first effective immunotherapies and the development of gene therapy. He is the first researcher to successfully insert foreign genes into humans.

<span class="mw-page-title-main">Ipilimumab</span> Pharmaceutical drug

Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

<span class="mw-page-title-main">Cancer immunology</span> Study of the role of the immune system in cancer

Cancer immunology (immuno-oncology) is an interdisciplinary branch of biology and a sub-discipline of immunology that is concerned with understanding the role of the immune system in the progression and development of cancer; the most well known application is cancer immunotherapy, which utilises the immune system as a treatment for cancer. Cancer immunosurveillance and immunoediting are based on protection against development of tumors in animal systems and (ii) identification of targets for immune recognition of human cancer.

<span class="mw-page-title-main">Tumor-infiltrating lymphocytes</span>

Tumor-infiltrating lymphocytes (TIL) are white blood cells that have left the bloodstream and migrated towards a tumor. They include T cells and B cells and are part of the larger category of ‘tumor-infiltrating immune cells’ which consist of both mononuclear and polymorphonuclear immune cells, in variable proportions. Their abundance varies with tumor type and stage and in some cases relates to disease prognosis.

Vaccine therapy is a type of treatment that uses a substance or group of substances to stimulate the immune system to destroy a tumor or infectious microorganisms such as bacteria or viruses.

CancerVax was an American pharmaceutical company founded in 1998 by Donald Morton. The company sought to develop a vaccine for cancer, and had candidates for melanoma reach phase III clinical trials. When those trials proved unsuccessful in 2005, the company soon underwent a reverse takeover with Micromet.

Adoptive cell transfer (ACT) is the transfer of cells into a patient. The cells may have originated from the patient or from another individual. The cells are most commonly derived from the immune system with the goal of improving immune functionality and characteristics. In autologous cancer immunotherapy, T cells are extracted from the patient, genetically modified and cultured in vitro and returned to the same patient. Comparatively, allogeneic therapies involve cells isolated and expanded from a donor separate from the patient receiving the cells.

Nicholas P. Restifo is an American immunologist, physician and educator in cancer immunotherapy. Until July 2019, he was a tenured senior investigator in the intramural National Cancer Institute of the National Institutes of Health at Bethesda, Maryland. Nicholas was an executive vice president of research at Lyell based in San Francisco.

Neuvenge, Lapuleucel-T, is a therapeutic cancer vaccine (TCV) in development by Dendreon (DNDN). It uses the "immunotherapy platform approach" first successfully demonstrated on the U.S. Food and Drug Administration (FDA)-approved TCV Provenge. It was first tested on breast cancer patients with tumors expressing HER2/neu, and is now scheduled to be tested on bladder cancer patients.

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Cancer/testis (CT) antigens are a group of proteins united by their importance in development and in cancer immunotherapy. In general, expression of these proteins is restricted to male germ cells in the adult animal. However, in cancer these developmental antigens are often re-expressed and can serve as a locus of immune activation. Thus, they are often classified as tumor antigens. The expression of CT antigens in various malignancies is heterogeneous and often correlates with tumor progression. CT antigens have been described in melanoma, liver cancer, lung cancer, bladder cancer, and pediatric tumors such as neuroblastoma. Gametogenesis offers an important role for many of these antigens in the differentiation, migration, and cell division of primordial germ cells, spermatogonia spermatocytes and spermatids. Because of their tumor-restricted expression and strong in vivo immunogenicity, CT antigens are identified as ideal targets for tumor specific immunotherapeutic approaches and prompted the development of several clinical trials of CT antigens-based vaccine therapy. CT antigens have been found to have at least 70 families so far, including about 140 members, most of which are expressed during spermatogenesis. Their expression are mainly regulated by epigenetic events, specifically, DNA methylation.

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References

  1. 1 2 "About". Ludwig Cancer Research. Archived from the original on 31 July 2015. Retrieved 4 August 2015.
  2. ↑ Weintraub, Karen (6 January 2014). "Six cancer centers to share $540 million research gift". USA Today. Archived from the original on 13 June 2016. Retrieved 4 August 2015.
  3. ↑ "Collaborative Areas". Ludwig Cancer Research. Archived from the original on 16 September 2015. Retrieved 4 August 2015.
  4. 1 2 Pace, Eric (29 August 1002). "Daniel Ludwig, Billionaire Businessman, Dies at 95". New York Times. Archived from the original on 13 July 2015. Retrieved 4 August 2015.
  5. ↑ Valdmanis, Richard (2014-01-06). "Billionaire Ludwig's estate donates $540 million for U.S. cancer research". Reuters. Archived from the original on 2021-07-17. Retrieved 2021-06-15.
  6. 1 2 Marshall, Eliot (6 January 2014). "A Billionaire's Final Gift to Six US Cancer Centers". Science. Archived from the original on 9 January 2014. Retrieved 4 August 2015.
  7. 1 2 3 4 Lane, Sir David (August 2014). "Trusting in Talent: How Daniel K. Ludwig's formula for success has fuelled four decades -- and counting -- of top-notch cancer research". Oncology News. Archived from the original on 24 March 2016. Retrieved 4 August 2015.
  8. ↑ Notter, John (10 April 2014). "Scientific Leaps Require Donors to Give Bigger". Chronicle of Philanthropy. Retrieved 4 August 2015.
  9. ↑ "New Paths of Discovery: 2012 Research Highlights" (PDF). Ludwig Cancer Research. Archived from the original (PDF) on 28 October 2015. Retrieved 4 August 2015.
  10. ↑ Lane, Sir David (24 March 2014). "Fighting Cancer With Smart Funding". Huffington Post. Archived from the original on 25 September 2015. Retrieved 4 August 2015.
  11. ↑ Old, Lloyd J.; et al. (October 1985). "Purification and characterization of a human tumor necrosis factor from the LuKII cell line". Proceedings of the National Academy of Sciences. 82 (19): 6637–6641. doi: 10.1073/pnas.82.19.6637 . PMC   391265 . PMID   3863119.
  12. ↑ Old, Lloyd J.; et al. (May 1979). "Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse". Proceedings of the National Academy of Sciences. 76 (5): 2420–2424. doi: 10.1073/pnas.76.5.2420 . PMC   383613 . PMID   221923.
  13. ↑ Coulie, Pierre G.; et al. (24 January 2014). "Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy". Nature Reviews Cancer. 14 (2): 135–146. doi:10.1038/nrc3670. PMID   24457417. S2CID   205469848.
  14. ↑ "Search results for "MAGE"". ClinicalTrials.gov. Archived from the original on 4 March 2016. Retrieved 12 August 2015.
  15. ↑ Gough, N.M.; et al. (March 1985). "Structure and expression of the mRNA for murine granulocyte-macrophage colony stimulating factor". The EMBO Journal. 4 (3): 645–653. doi:10.1002/j.1460-2075.1985.tb03678.x. PMC   554237 . PMID   3874057.
  16. ↑ Davenport, Liam (28 May 2015). "Injectable T-VEC Offers Hope to Melanoma Patients". Medscape. Archived from the original on 23 April 2016. Retrieved 12 August 2015.
  17. ↑ Villa, L.L. (November 2007). "Overview of the clinical development and results of a quadrivalent HPV (types 6, 11, 16, 18) vaccine". International Journal of Infectious Diseases. 11 (Suppl 2): S17–25. doi: 10.1016/S1201-9712(07)60017-4 . PMID   18162241.
  18. ↑ Hodi, F. Stephen; et al. (19 August 2010). "Improved Survival with Ipilimumab in Patients with Metastatic Melanoma". The New England Journal of Medicine. 363 (8): 711–723. doi:10.1056/NEJMoa1003466. PMC   3549297 . PMID   20525992.
  19. ↑ Wolchok, J.D.; et al. (1 December 2009). "Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria". Clinical Cancer Research. 15 (23): 7412–7420. doi: 10.1158/1078-0432.CCR-09-1624 . PMID   19934295.
  20. ↑ Katso, R.; et al. (2001). "Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer". Annual Review of Cell and Developmental Biology. 17: 615–675. doi:10.1146/annurev.cellbio.17.1.615. PMID   11687500.
  21. ↑ Vogelstein, Bert; et al. (29 March 2013). "Cancer Genome Landscapes". Science. 339 (6127): 1546–1558. doi:10.1126/science.1235122. PMC   3749880 . PMID   23539594.
  22. ↑ "Leadership". Ludwig Cancer Research. Archived from the original on 4 August 2015. Retrieved 8 August 2015.
  23. ↑ "John L. Notter". Conrad N. Hilton Foundation. Archived from the original on 9 July 2015. Retrieved 8 August 2015.
  24. ↑ "Edward McDermott Jr". Ludwig Cancer Research. Archived from the original on 27 August 2015. Retrieved 8 August 2015.
  25. ↑ "Press Release". Archived from the original on 6 February 2017. Retrieved 5 February 2017.
  26. ↑ "Peter Ratcliffe Nobel Prize facts". www.nobelprize.org. Retrieved 18 April 2024.
  27. 1 2 "Lucy Shapiro Lab". Ludwig Cancer Research. Retrieved 16 April 2024.
  28. ↑ "The President's National Medal of Science: Recipient Details". National Science Foundation. Archived from the original on 5 March 2016. Retrieved 15 August 2015.
  29. 1 2 "M.I.T. Center". Ludwig Cancer Research. Retrieved 16 April 2024.
  30. ↑ "The President's National Medal of Science: Recipient Details". National Science Foundation. Archived from the original on 5 March 2016. Retrieved 15 August 2015.
  31. ↑ "Member Directory". National Academy of Sciences. Archived from the original on 26 March 2017. Retrieved 15 August 2015.
  32. ↑ "Web Cavenee Lab". Ludwig Cancer Research. Archived from the original on 6 August 2015. Retrieved 15 August 2015.{{cite web}}: CS1 maint: unfit URL (link)
  33. ↑ "Don Cleveland Lab". Ludwig Cancer Research. Archived from the original on 12 December 2018. Retrieved 15 August 2015.{{cite web}}: CS1 maint: unfit URL (link)
  34. ↑ "Richard Kolodner Lab". Ludwig Cancer Research. Archived from the original on 7 October 2015. Retrieved 15 August 2015.{{cite web}}: CS1 maint: unfit URL (link)
  35. ↑ "MSK Center". Ludwig Cancer Research. Retrieved 16 April 2024.
  36. ↑ "Stanford Center". Ludwig Cancer Research. Retrieved 16 April 2024.
  37. ↑ "Johns Hopkins Center". Ludwig Cancer Research. Retrieved 16 April 2024.
  38. ↑ "Harvard Center". Ludwig Cancer Research. Retrieved 16 April 2024.
  39. ↑ "Fellows Directory". The Academy of Medical Sciences. Archived from the original on 10 August 2015. Retrieved 15 August 2015.
  40. ↑ "Xin Lu Lab". Ludwig Cancer Research Oxford. Retrieved 16 April 2024.
  41. ↑ "Peter Ratcliffe Lab". Ludwig Cancer Research Oxford. Retrieved 16 April 2024.
  42. 1 2 "Locations". Ludwig Cancer Research. Retrieved 16 April 2024.
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