Mike Clark
"An antibody engineer who also enjoys the mountains."
mrc7@cam.ac.uk
Mike's home-page
© Mike Clark, PhD., Cambridge University, UK
Last updated on 8th September 2005
The following links are to other sites with relevant information on the commercial and therapeutic exploitation of monoclonal antibodies which derive from the Department of Pathology, Cambridge University. The links are to accompany my own discussions of these topics.
Before following any of the links please do remember to book mark this site so that you can easily return again.
I would also ask you to please note that I am unable to offer any kind of advice for those seeking treatment or clinical advice on new therapies. I would direct these people firstly to their own medical advisors. There may however be information on the sites linked through from here as to the status eg approved, or still in clinical trials, of the antibodies discussed.
This department i.e. the Department of Pathology, Cambridge University is where much of the work on therapeutic antibodies such as CAMPATH-1 was carried out between the years 1979 and 1994. The name CAMPATH derives obviously from CAMbridge PATHology and it has now become a registered trademark for the CD52 antibody CAMPATH-1H, which was developed by the startup US Biotech Company LeukoSite Inc and following a series of company acquisitions is now being developed by Genzyme Oncology.
During the early years of the CAMPATH projects the Division of Immunology, within the Pathology Department, was headed by Professor Robin Coombs, who is well known for having developed the passive antiglobuln test or 'Coombs test', used for the diagnosis of anti-RhD antibodies important in Haemolytic Disease of the Newborn (HDN). Another key member of the Division at that time was Dr Alan Munro, Reader in Immunology, who collaborated on the early derivation of some of the therapeutic antibodies and who later left the University in about 1990 to found the Cambridge biotech startup company, Immunology Ltd which later developed into the company Cantab Pharmaceuticals Plc, now part of Xenova Plc
I (Mike Clark) joined Pathology after completing my PhD (1978-1981) under the supervision of Dr Cesar Milstein at the MRC Laboratory of Molecular Biology and was a member of Professor Waldmann's group here in the Pathology Department from 1981 until I was appointed to a Lectureship in this same Department in 1990. Since 1990 I have continued to work here in Pathology on therapeutic applications of antibodies including the engineering of antibodies with modified effector functions(see my links below).
Professor Herman Waldmann, left his personal chair in the Department of Pathology, Cambridge University, to take up the Chair of Pathology at the Sir William Dunn School of Pathology, Oxford University. With him went some of the key researchers involved in his antibody based research programmes including Steve Cobbold and Geoff Hale. Also the Therapeutic Antibody Centre which had been based at the Blood Transfusion Centre, Addenbrooke's Hospital Cambridge, closed, and a new centre was established in 1995 on the Churchill Hospital site in Oxford. The links below provide information on these.
LeukoSite was a USA based biotechnology company which had taken up the license for CAMPATH-1H after Glaxo-Wellcome abandoned the project. One of the founding scientists behind LeukoSite, Professor Timothy Springer, was a visiting scientist to the Cambridge University, Department of Pathology, in the mid 70s, working in the same laboratories as Dr Alan Munro and Dr Herman Waldmann. Both Timothy Springer and Herman Waldmann changed their research directions when they decided to learn the new technology of making monoclonal antibodies from hybridomas published by Köhler and Milstein in Nature, in 1975, from the MRC Laboratory of Molecular Biology, Cambridge.
In October of 1999 LeukoSite Inc and Millennium Pharmaceuticals announced a merger. In April 2000 Millennium announced that they had filed a Biologics Licensing Application in the USA and a Marketing Authorisaton Application in Europe for CAMPATH® (alemtuzumab).
On the 8th May 2001 Millennium announced "The U.S. Food and Drug Administration (FDA) today cleared Campath® (alemtuzumab) humanized monoclonal antibody for marketing as a treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL) who have been treated with alkylating agents and have failed fludarabine therapy."
A marketing partnership was set up between Millennium and several other companies and then later the rights in Campath® were transferred to Ilex Oncology Inc. Further information can be found out at the following web addresses
Ilex Oncology entered into a partnership arrangement with Millennium Pharmaceuticals for the marketing and continued development of Campath®. Following the successful approval of the antibody by the FDA, Ilex acquired the full rights from Millennium. Later, in December 2004, Genzyme completed the acquisition of Ilex Oncology renaming this division as Genzyme Oncology.
Following the acquisition of Ilex Oncology Inc in December 2004, Campath® (alemtuzumab) is now a marketed product of Genzyme Oncology.
This Cambridge based biotechnology company was founded by Dr Alan Munro after he left the Department of Pathology. One of the early products in development was a synergistic pair of CD45 antibodies from Herman Waldmann's laboratory to be used to reduce the problems of organ graft rejection. This project was abandoned by Cantab after disappointing results from the US trials and the company was then best known for it's anti-virus vaccine work. Interestingly the European trials of the CD45 antibodies resulted in more optimistic findings and it may be that the differences in clinical practice in the US and Europe had a bearing on the outcome of the trials.
In 2001 Cantab Pharmaceuticals merged with Xenova to form the Xenova Group plc.
This organization originally started out as a combination of the UK Government agencies known as the National Research and Development Corporation (NRDC) and the National Enterprises Board (NEB). It was later privatised under the name British Technology Group and is now known as simply BTG. Under guidelines then in operation for MRC funded research projects, many of the therapeutic antibodies, including CAMPATH-1, which were developed in the Department of Pathology, Cambridge University, were assigned to BTG through the University's Wolfson Industrial Liaison Office.
The Wolfson Industrial Liaison Office was the Cambridge University Technology Transfer Office which has been responsible for handling the assignments of the various therapeutic antibodies and the associated intellectual property rights. The actual agreements are assigned by the University in the names of Lynxvale Ltd and CUTS Ltd (Cambridge University Technical Services). The office of WILO was merged into a new organization called the Research Services Division, and technology transfer was then conducted by the Technology Transfer Office within RSD. More recently the role of technology transfer has again been separated from RSD and is carried out under the name of Cambridge Enterprise.
The Medical Research Council was the major funding agency responsible for supporting the various programmes and projects underway in the Department of Pathology which led to the development of antibodies such as CAMPATH-1H. In particular they awarded Herman Waldmann two successive 5 year programme grants 1981-1991 for work on the Immunobiology of Bone Marrow Transplantation and also supported the Cambridge based Therapeutic Antibody Centre at Addenbrooke's Hospital. They then continued to support Herman Waldmann's research upon his move to the Sir William Dunn School of Pathology Oxford in 1993.
This is of course a key link in the whole chain. César Milstein and George Köhler did their pioneering work on establishing monoclonal antibodies in this MRC Institute and published the results in the journal, Nature in 1975. They were later to receive the Nobel Prize for Medicine for this important work. Many individuals went to César Milstein in the late 70s to learn the hybridoma technology, among them being Timothy Springer and Herman Waldmann.
I (Mike Clark) was a PhD student with César Milstein from 1978-1981 and first met Herman Waldmann in 1978 when he was on sabbatical leave in César Milstein's laboratory. We were both present in the laboratory when the rat myeloma cell line Y3/Ag1.2.3 was developed by Bruce Wright and Giovanni Galfré, for use in making rat monoclonal antibodies, and hence we were amongst the first in the world to work with rat hybridomas. The original hybridomas in the CAMPATH series were all from a cell fusion involving the Y3Ag 1.2.3 cell line.
Another member of LMB who joined in the late 70s was Michael Neuberger. He was just establishing systems for the expression of recombinant immunoglobulin genes and later published one of the worlds first chimaeric antibodies. Michael also collaborated with another LMB scientist Greg Winter on the NP V-region humanisation project and of course it was a collaboration between myself in Herman Waldmann's laboratory, in the Pathology Department, and Lutz Riechmann in Greg Winter's laboratory in LMB, which resulted in the worlds first fully humanised monoclonal antibody for therapy CAMPATH-1H.
The text and illustrations on this web page are © copyright 2000, 2001, 2002, 2005 M.R. Clark, PhD., Lecturer in Therapeutic and Molecular Immunology, Department of Pathology, Cambridge University, Cambridge UK CB2 1QP. The information provided is to the best of my knowledge correct but if you are aware of any errors please do contact me.
Mike Clark