An article from the "Immunotherapy and Antigen presentation" research group - led by Johanna Olweus, Head of Department of Immunology at the Institute for Cancer Research - has recently been published in the highly rated journal "Leukemia" (journal impact factor 8.3).
The paper is entitled "Targeting B cell leukemia with highly specific allogeneic T cells with a public recognition motif". The first author is Ingerid Weum Abrahamsen.
Here, they present data demonstrating that T cells can be identified and selected that specifically kill cancer cells from patients with chronic lymphocytic leukemia. The results bear promise that graft-versus-leukemia effects can be achieved in the absence of graft-versus-host disease.
T cells have the ability to cure infections without side effects. The reason is that they express receptors that can recognize protein fragments (peptides) from foreign antigens with a high degree of specificity. In patients who have developed cancer, the immune system normally fails at attacking the cancer cells, as the malignant cells are not recognized as foreign and dangerous. In contrast, T cells from a healthy donor may see the cancer cells in a patient as foreign, due to genetic differences between donor and patient. This is an important reason for the potentially curative effects of stem cell transplantation in leukemia and lymphoma treatment - as T cells are included in the transplant. The effect is called graft-versus-leukemia/lymphoma. The problem is that T cells often recognize and kill also normal cells, thereby causing graft-versus-host disease, which may lead to serious complications and in worst case death.
Olweus and co-workers have developed a novel method that allows T cells that mediate a selective "graft-versus-leukemia" effect to be identified and isolated. These T cells have the ability to kill with a high degree of specificity, by recognizing proteins selectively expressed in certain cell types. Such T cells are normally not found in the circulation, and auto-immunity is thereby avoided. The T cells are introduced to peptides from normally expressed proteins in complex with a foreign HLA molecule, in cell culture. By this approach, T cells were generated from healthy donors with the ability to kill cancer cells from patients with chronic lymphatic leukemia specifically and efficiently. The T cells recognize peptides from the B cell specific protein CD20.
Therapeutic antibodies represent one of the fastest growing classes of drugs in the pharmaceutical industry today. The results are promising, even though few patients are cured so far. The antibodies are directed against cell type specific proteins, and not againts cancer specific proteins, which are more difficult to identify. The Olweus research group aims to apply the same principle to T cell based immunotherapy. T cells kill by other mechanisms than antibodies and chemotherapy and may therefore be efficatious where other therapeutic regimens fail, or act in synergy. T cells can furthermore recognize intracellular proteins, thereby increasing the number of potential therapeutic goals dramatically (relative to antibodies), as most proteins are intracellular.
Johanna Olweus is professor, and leader of the research group "Immunotherapy and Antigen presentation” in the Department of Immunology at the Institute for Cancer Research. The group is aiming at generating new forms of T cell based immunotherapy against cancer.
The MDs Ingerid W. Abrahamsen and Erlend Strønen played important roles in the development of the new method, and Abrahamsen performed the majority of the cell culture work to generate the T cells that kill malignant B cells. Scientist Sébastien Wälchli was central for the development of the assay for identifying the T cell receptor sequences, and for the discovery of the public recognition motif. This translation research project was conducted in collaboration with Fridtjof Lund-Johansen and clinicians at Oslo University Hospital, as well as professor Tom Schumacher in Amsterdam, who is in the international forefront in tumor immunology.
Targeting B cell leukemia with highly specific allogeneic T cells with a public recognition motif.
Abrahamsen IW, Stronen E, Wälchli S, Johansen JN, Kjellevoll S, Kumari S, Komada M, Gaudernack G, Tjonnfjord G, Toebes M, Schumacher TN, Lund-Johansen F, Olweus J.
Leukemia. 2010 Sep 16
PubMed - Leukemia web site
Home page of the Johanna Olweus group - Immunotherapy and Antigen presentation