- Trifari S, Kaplan CD, Tran EH, Crellin NK, Spits H, Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. NAT IMMUNOL 2009;10 (8):864-871 [PubMed]
- Bernink JH, Peters CP, Munneke M, te Velde AA, Meijer SL, Weijer K, Hreggvidsdottir HS, Heinsbroek SE, Legrand N, Buskens CJ, Bemelman WA, Mjösberg JM, Spits H, Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. NAT IMMUNOL 2013;14 (3):221-229 [PubMed]
- Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, Koyasu S, Locksley RM, McKenzie ANJ, Mebius RE, Powrie F, Vivier E, Innate lymphoid cells--a proposal for uniform nomenclature. NAT REV IMMUNOL 2013;13 (2):145-149 [PubMed]
- Artis D, Spits H, The biology of innate lymphoid cells. NATURE 2015;517 (7534):293-301 [PubMed]
- Mjösberg JM, Trifari S, Crellin NK, Peters CP, van Drunen CM, Piet B, Fokkens WJ, Cupedo T, Spits H, Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. NAT IMMUNOL 2011;12 (11):1055-1062 [PubMed]
Dr. Spits has a 35 years-spanning career in both academia and industry. He is a professor of Cell Biology at the Academic Center of the University of Amsterdam (AMC) where he leads a research program on auto immune- and inflammatory diseases. He is also a founder of AIMM Therapeutics, a company that develops human monoclonal antibodies for treatment of diseases with a high unmet medical need and serves as its CSO since its inception. Previously Dr. Spits was a Senior Director at Genentech where he implemented and directed drug discovery in the Cancer Immunotherapy area and led the large molecule drug discovery efforts in the area of auto immune- and inflammatory diseases. Before joining Genentech Dr. Spits was professor Cell Biology at the AMC. Prior to that Dr. Spits was at the Netherlands Cancer Institute where he was a senior staff scientist and served as Head of the Immunology Department. From 1985 through 1992 Dr. Spits held several positions at Schering-Plough, first at the Schering–Plough Institute for Immunological Research in Lyon and then at the DNAX Research Institute for Molecular Biological Research in Palo Alto in California. Dr. Spits earned his PhD degree at the University of Amsterdam and conducted research at the Dana Farber Institute for Cancer Research, Harvard University. He authored more than 300 peer-reviewed scientific publications.
During his career Spits has made important contributions to the field of human lymphocytes. He was the first (in 1985) to describe the phenomenon of redirected killing by human T cells using anti CD3 antibodies. This breakthough discovery forms the basis of therapeutic bispecific antibodies that are currently tested in the clinic for treatment of various forms of cancer. When at DNAX he was one of the first to describe human Th1 clones. He studied the mechanisms of human T cell development and identified a number of previously not recognized intermediate cell stages in human thymic development. More recent contributions include the first description of Th22 and the discovery of human Lymphoid Tissue inducer cell and various other human Innate Lymphoid cell subsets. While studying the mechanisms of development of human antibody-producing B cells his lab invented an innovative technology to immortalize human and non-human antibody-producing B cells which was used by the company AIMM therapeutics to establish a number of broadly reacting highly neutralizing virus specific antibodies, some of which are in clinical development. Currently Spits investigates the function of Innate lymphoid cells at mucosal tissues, in particular lung and gut. In addition he works in the field of tumor immunology. One of his projects aims to generate therapeutic human monoclonal antibodies against melanoma. His research is supported by various grants including a 5 year advanced grant of the European Research Council.
Spits has been named a 2015 Thomson Reuters Highly Cited Reseacher (ranked among the top 1% of researchers of most cited documents in their specific field)
The biology of human Innate Lymphoid Cells and B cells. Antibodies against tumor antigens
Targeting human rhinoviruses and group 2 ILC in asthma exacerbations
Asthma constitutes a group of debilitating chronic diseases that affects millions of people worldwide, profoundly impacting patient quality of life and incurring large costs in terms of treatment and lost productivity. In particular so called asthma exacerbations induced by respiratory viruses such as human Rhinovirus and respiratory syncytial virus present significant unmet medical need. Successful discovery and development of more effective therapies to treat asthma exacerbations depends first on a better understanding of the underlying mechanisms, including how proinflammatory cells proliferate unchecked, and how the body’s own mechanisms might be enlisted to control inflammation and second on inhibition of exacerbating respiratory viruses. My group is addressing this challenge in two ways. First, we have discovered and characterized populations of innate lymphoid cells (ILCs) including ILCs that produce high amounts of Th2 cytokines (ILC2) and demonstrated amplified numbers of these cells in inflamed nose polyps in rhinosinusitis, a chronic type 2 inflammatory disease. Second, our group has developed a technological breakthrough that permits the establishment of clonal, antigen-specific human B cell lines using a unique genetic reprogramming technology. Using this technology we have generated broadly reacting, highly neutralizing, human monoclonal antibodies against respiratory syncytial virus and influenza virus. We hypothesize that ILC2 activated by respiratory viruses are key players in asthma exacerbations induced by these viruses and are therefore compelling targets for effective therapies for asthma. Our objectives are to identify the key drivers of function of ILC2 and to develop broadly reacting highly neutralizing antibodies against human rhinovirus (HRV) which accounts for the majority of asthma exacerbations. In addressing these objectives, we make use of extensive expertise in fundamental human immunology with groundbreaking, translational approaches using human tissue biopsy samples, state-of-the-art in vitro techniques, and a human immune system mouse model developed by our laboratory that permits in vivo study of the human immune system.
ILC in the human Intestine
ILC play important roles in innate immunity, maintenance of tissue homeostasis and tissue repair after damage inflicted by pathogens. Our group investigates development and function of ILC populations present in different compartnments present in non-inflamed intestine and in intestines of patients suffering Inflammatory Bowel diseases, in particular Crohn's disease and Ulcerative Colitis. The ultimate goal is to determine whether these cells play a role in the pathology. If so the knowledge acquired in this project can result in new therapies targeting ILC.
Characterization of immortalized human B cells
We have developed a highly efficient platform to generate human monoclonal antibodies. The platform uses B cells immortalized by genetic modification. We also have set up a mouse model with a rudimentary human immune system; the so called human immune system (HIS) mouse. B cells develop in these mice but those cells do not mature. In this project we investigate how we can optimise B cell maturation in HIS. If successful this project will provide tools to optimally test the response of human immune cells against vaccines in vivo and to make fully human monoclonal antibodies against clinical targets following immunization.
Human monoclonal antibodies against tumor antigens
Immunotherapies such as treatment with checkpoint inhibitors such as antibodies against PD-1 and CTLA4 have a major impact on survival in a number of cancers, particular melanoma. Whereas the role of T cells in the immuneresponse against cancer cells following checkpoint inhibition is well established, the role of B cells and the antibodies they produce has not yet been systematically studied. We hypothesize that B cells of patients who successfully respond to immunotherapy produce antibodies that contribute to the tumor free status of these patients. Such antibodies may have therapeutic utility. In collaboration with Dr Mette Hazenberg of the department of Hematology, Dr Rosalie Luiten of the department of dermatology of the AMC and the AMC spin out company AIMM Therapeutics we establish B cell clones from patients with a durable remission following immunotherapy. We focus on Melanoma patients tretead with cellular therapies or with checkpoint inhibitors and on Acute Myeloid Leukemia patients treated with allogeneic stem cell transplatation. From peripheral blood B cells of these patients we establish immortalized B cell clones and screen these clones for production of antibodies that specifically react with tumor cells. A number of tumor-specific antibodies have been generated which are now tested for their potential to reduce tumor growth
Prof. dr. H. Spits
Dr. S.M. Bal PhD
Dr. J.M. Bernink MSc
Dr. J.R. Fergusson
Drs. K. Golebski
Dr. B.A. Heesters
Dr. J. Romero-Ros
Dr. M.M. Shikhagaie PhD
Drs. G. de Jong MD (AIMM Therapeutics)
Y.F. van Lier
S.J.L. Merat MSc
- Scientific manager, AIMM therapeutics
- Europese Unie
- Janssen Research & Development, LLC
- Universiteit Leiden
- ZonMw (Vrijgesteld)