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Author: Gordon B. Mills Publisher: National Library of Canada ISBN: 9780315193796 Category : Interleukin-2 Languages : en Pages : 0
Book Description
In order to respond to a foreign challenge, cells of the immune system must recognize the pathogen as foreign and must also receive a "second signal'. Both signals are required to induce the proliferation and differentiation of effector cells. Malignant disease in the otherwise immunocompetent host could escape immune control through failure to recognize tumor cells as foreign or through lack of the required "second signal". Previous work suggested that Interleukin 2 may be one of the second signals stimulating immune cells. Failure of Interleukin 2 production or action may allow malignant cells to escape the immune system. Therefore, an attractive method of immunotherapy would be to increase the positive immunoregulatory action of IL2 in vivo. Unfortunately, methods for modulating Interleukin action in vivo are not available. Therefore, removing lymphocytes from tumor-bearing mice, culturing them with exogenous Interleukin 2 and, subsequently, reinfusing the programed cells into tumor-bearing mice was explored as a model of a possible immunotherapeutic technique. Spleen cells from tumor-bearing mice contain populations of precursor cells reactive to autologous tumor. Culture of these cells with exogenous Interleukin 2 generated a population of helper lymphocytes able to recruit host anti-tumor activity. Culture with IL2 also generated two populations of lymphocytes directly cytotoxic to tumor cells. One of the populations of cytotoxic lymphocytes, generated by culture with Interleukin 2 and autologous tumor, was relatively specific to the sensitizing tumor. These are probably "classical" cytotoxic T lymphocytes. The second population of cytotoxic cells, generated by culture with Interleukin 2 alone, demonstrated a broader spectrum of anti-tumor reactivity. Identifying the origin of the cell responsible for this non-specific activity has proven to be difficult. The broad spectrum of activity, the lack of requirement for antigen sensitization, and the lack of H2 restriction are appropriate for "natural killer" cells; whereas, the time course of activation and the surface marker phenotype are appropriate for "classical" cytotoxic lymphocytes. The precursors of both cytolytic cell populations, described above, are significantly increased in tumor-bearing animals. This suggests that tumor recognition occurs in tumor-bearing animals but that the "second signal" required for proliferation and differentiation is not present or not received. Interleukin 2 can provide this signal at least in vitro. Culture of peripheral blood cells from ovarian cancer patients with either human IL2 or murine IL2 generated cytotoxic lymphocytes which were active against autologous tumor. In the immunotherapy of murine tumors, the cytotoxic lymphocyte containing populations were most effective if given shortly after injection of the tumor. The response was dose related. Repeated injections were more effective than single injections. The cultured cells homed poorly to the tumor, therefore injection directly into the tumor site was more effective than intravenous administration. Therapy with cytotoxic lymphocytes was synergistic with surgical therapy of CaD2 tumors. Therapy with cytotoxic lymphocyte containing populations consistently improved the survival of mice with intraperitoneal P815 tumors. Despite the improved survival of mice following therapy, there were few long term survivors. Therapy with cytotoxic lymphocyte containing populations cured some mice with subcutaneous P815 tumors. The mice that died of the tumor did not demonstrate an improvement in survival times compared to untreated mice. Mice cured of the P8 15 tumor by treatment with cytotoxic lymphocyte containing preparations remain tumor-immune. There were no significant detrimental side effects of therapy with cytotoxic lymphocytes.
Author: Gordon B. Mills Publisher: National Library of Canada ISBN: 9780315193796 Category : Interleukin-2 Languages : en Pages : 0
Book Description
In order to respond to a foreign challenge, cells of the immune system must recognize the pathogen as foreign and must also receive a "second signal'. Both signals are required to induce the proliferation and differentiation of effector cells. Malignant disease in the otherwise immunocompetent host could escape immune control through failure to recognize tumor cells as foreign or through lack of the required "second signal". Previous work suggested that Interleukin 2 may be one of the second signals stimulating immune cells. Failure of Interleukin 2 production or action may allow malignant cells to escape the immune system. Therefore, an attractive method of immunotherapy would be to increase the positive immunoregulatory action of IL2 in vivo. Unfortunately, methods for modulating Interleukin action in vivo are not available. Therefore, removing lymphocytes from tumor-bearing mice, culturing them with exogenous Interleukin 2 and, subsequently, reinfusing the programed cells into tumor-bearing mice was explored as a model of a possible immunotherapeutic technique. Spleen cells from tumor-bearing mice contain populations of precursor cells reactive to autologous tumor. Culture of these cells with exogenous Interleukin 2 generated a population of helper lymphocytes able to recruit host anti-tumor activity. Culture with IL2 also generated two populations of lymphocytes directly cytotoxic to tumor cells. One of the populations of cytotoxic lymphocytes, generated by culture with Interleukin 2 and autologous tumor, was relatively specific to the sensitizing tumor. These are probably "classical" cytotoxic T lymphocytes. The second population of cytotoxic cells, generated by culture with Interleukin 2 alone, demonstrated a broader spectrum of anti-tumor reactivity. Identifying the origin of the cell responsible for this non-specific activity has proven to be difficult. The broad spectrum of activity, the lack of requirement for antigen sensitization, and the lack of H2 restriction are appropriate for "natural killer" cells; whereas, the time course of activation and the surface marker phenotype are appropriate for "classical" cytotoxic lymphocytes. The precursors of both cytolytic cell populations, described above, are significantly increased in tumor-bearing animals. This suggests that tumor recognition occurs in tumor-bearing animals but that the "second signal" required for proliferation and differentiation is not present or not received. Interleukin 2 can provide this signal at least in vitro. Culture of peripheral blood cells from ovarian cancer patients with either human IL2 or murine IL2 generated cytotoxic lymphocytes which were active against autologous tumor. In the immunotherapy of murine tumors, the cytotoxic lymphocyte containing populations were most effective if given shortly after injection of the tumor. The response was dose related. Repeated injections were more effective than single injections. The cultured cells homed poorly to the tumor, therefore injection directly into the tumor site was more effective than intravenous administration. Therapy with cytotoxic lymphocytes was synergistic with surgical therapy of CaD2 tumors. Therapy with cytotoxic lymphocyte containing populations consistently improved the survival of mice with intraperitoneal P815 tumors. Despite the improved survival of mice following therapy, there were few long term survivors. Therapy with cytotoxic lymphocyte containing populations cured some mice with subcutaneous P815 tumors. The mice that died of the tumor did not demonstrate an improvement in survival times compared to untreated mice. Mice cured of the P8 15 tumor by treatment with cytotoxic lymphocyte containing preparations remain tumor-immune. There were no significant detrimental side effects of therapy with cytotoxic lymphocytes.
Author: J. Wagstaff Publisher: Springer Science & Business Media ISBN: 9401117535 Category : Medical Languages : en Pages : 195
Book Description
Recombinant human interleukin-2 became available for clinical use in the mid 1980s. Recent years have seen an enormous amount of clinical research with this cytokine and interleukin-2 has now been registered for use in a number of European countries for the treatment of metastatic renal cell carcinoma. This book is designed to provide the clinical oncologist wishing to use interleukin-2 with a basic background concerning the biology of the agent, a discussion concerning practical aspects, of its clinical use including management of toxicity and an overview of the clinical results together with a description of how this internesting cytokine might be developed in the future.
Author: Eva Lotzova Publisher: CRC Press ISBN: 1351090690 Category : Science Languages : en Pages : 556
Book Description
This is the first-and only-publication available which provides the most recent information in this particular field of biomedicine. Interleukin-2 (IL-2) and IL-2 activated killer cells have been shown to have a potential in the treatment of a variety of human malignant diseases. This work comprehensively summarizes basic aspects of IL-2 as well as its clinical application, therefore making all these aspects easily accessible to the readers. Because of the clinical significance of this molecule in the treatment of cancer, the basic and clinical investigations in the IL-2 field are rapidly expanding, together with the interest of the scientific and medical community. This book is an excellent educational and teaching tool for scientists, clinicians, and students. Those who already have expertise in research in the IL-2 area will find this reference indispensible.
Author: Kendall A Smith Publisher: Elsevier ISBN: 0323139949 Category : Medical Languages : en Pages : 334
Book Description
Interleukin 2 focuses on interleukin 2 (IL-2) and its impact on immunology. Topics covered include IL-2's mechanism of action, the structure of the IL-2 receptor, the characteristics of natural and recombinant human IL-2, regulation of IL-2 production by the T cell antigen receptor, how IL-2 binding induces the transcription of a novel set of genes, and the pathological roles of IL-2 receptor inducers in adult T cell leukemia. This book is comprised of 12 chapters and begins with a historical overview of IL-2, from the discovery of soluble mitogenic factors in culture media of stimulated lymphocytes to the discovery of IL-2 as the molecule responsible for stimulating T cell proliferation. The physicochemical and biological properties of purified recombinant IL-2 are then described, paying particular attention to natural IL-2 derived from human peripheral blood leukocytes. The chapters that follow discuss the different techniques used to gain insight into the functionally important regions of IL-2, the role of the T cell antigen receptor in regulating the production of IL-2, and the structure of the human high-affinity IL-2 receptor. The book also describes transmembrane signaling by IL-2, IL-2-inducible gene expression in T lymphocytes, abnormal IL-2 receptor expression in adult T cell leukemia, the use of IL-2 receptors in immunosuppressive therapy, and the use of IL-2 as a pharmacologic reagent. This book will be of interest to students and researchers in immunology and biochemistry.
Author: Robert C. Rees Publisher: IRL Press ISBN: Category : Medical Languages : en Pages : 208
Book Description
The molecular structure of interleukin-2 (IL-2) and that of its receptor subunits provide a basis for understanding lymphocyte activation by IL-2 and the generation of effector cells capable of mediating cytotoxicity towards tumors. This book provides an up-to-date account of IL-2, its effect on lymphocyte function, and clinical applications. Internationally know experts review the molecular aspects of cell signalling, giving insight on the in vivo pathways of activation likely to be important in determining clinical responses. They also examine the use of cytokines, particularly IL-2, in the treatment of cancer, and describe the results of recent clinical trials using IL-2, as well as of adoptive cell therapy. Providing a clear account of recent progress, the book also reviews the problems involved in attempting to improve the therapeutic benefit of IL-2, along with the importance of mechanisms which subverse IL-2 responses. This is the most up-to-date account of molecular research and clinical trials in this area, and will be of great benefit to students and researchers in immunology, pharmacology, biochemistry, and oncology who are interested in this vitally important topic.
Author: Shuning Gai Publisher: ISBN: Category : Languages : en Pages : 113
Book Description
Mobilizing the immune system to recognize and destroy tumor cells is a promising strategy for treating cancer. In contrast to standard therapeutic approaches such as surgery, radiation, and chemotherapy, immunotherapy offers the possibility of systemic yet tumor-specific cell killing as well as long-lasting cancer protection. A significant mode of tumor rejection is direct tumor cell killing by immune cells, such as cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. These cell types are stimulated to proliferate by the cytokine interleukin-2 (IL-2). Consequently, IL-2 has been actively pursued as an agent for immunotherapy, either alone or in combination with other therapeutic strategies. IL-2 is characterized by rapid systemic clearance, with a fast-phase serum half-life of 13 minutes and a slow-phase half-life of 85 minutes. We hypothesized that prolonging the persistence of IL-2 at the cell surface or extending its circulation lifetime would increase its immunostimulatory potency. Therefore, we evolved murine IL-2 to bind the alpha subunit of its receptor, known as IL-2Ra or CD25, with 500-fold higher affinity; tethered IL-2 to the surface of T cells via streptavidin sandwiches; and fused IL-2 to the antibody Fc fragment, designated Fc/ IL-2, which extended the slow-phase serum half-life by 15 hours. Compared to free IL-2, Fc/IL-2 fusions induced superior control of solid tumors in mice. Interestingly, combining Fc/IL-2 with an anti-tumor antibody led to potent suppression of tumor growth during treatment. Furthermore, combination therapy protected two of three mice from subsequent tumor re-challenge. Depletion of CTLs or NK cells completely or partially, respectively, abrogated treatment efficacy, suggesting these immune cell types contribute to the anti-tumor response. In the context of Fc fusion, increasing the affinity of IL-2 for CD25 did not further improve efficacy. Ablation of CD25 binding, however, significantly reduced efficacy and also increased treatment toxicity. Since we employed a mutant Fc with disrupted FcyR binding, and hence reduced effector function, and fused IL-2 to mutant Fc monovalently, the significant therapeutic benefit of Fc/IL-2 over free IL-2 likely results from the extension of IL-2 circulation lifetime. We hypothesize that long-circulating IL-2 would potently synergize with other anti-tumor antibodies for effective cancer immunotherapy.
Author: Tony Romeo Publisher: Springer Science & Business Media ISBN: 3540754180 Category : Medical Languages : en Pages : 302
Book Description
Throughout the biological world, bacteria thrive predominantly in surface-attached, matrix-enclosed, multicellular communities or biofilms, as opposed to isolated planktonic cells. This choice of lifestyle is not trivial, as it involves major shifts in the use of genetic information and cellular energy, and has profound consequences for bacterial physiology and survival. Growth within a biofilm can thwart immune function and antibiotic therapy and thereby complicate the treatment of infectious diseases, especially chronic and foreign device-associated infections. Modern studies of many important biofilms have advanced well beyond the descriptive stage, and have begun to provide molecular details of the structural, biochemical, and genetic processes that drive biofilm formation and its dispersion. There is much diversity in the details of biofilm development among various species, but there are also commonalities. In most species, environmental and nutritional conditions greatly influence biofilm development. Similar kinds of adhesive molecules often promote biofilm formation in diverse species. Signaling and regulatory processes that drive biofilm development are often conserved, especially among related bacteria. Knowledge of such processes holds great promise for efforts to control biofilm growth and combat biofilm-associated infections. This volume focuses on the biology of biofilms that affect human disease, although it is by no means comprehensive. It opens with chapters that provide the reader with current perspectives on biofilm development, physiology, environmental, and regulatory effects, the role of quorum sensing, and resistance/phenotypic persistence to antimicrobial agents during biofilm growth.
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Author: Gordon B. Mills
Author: J. Wagstaff
Author: Eva Lotzova
Author: Kendall A Smith
Author: Robert C. Rees
Author: Mulin Ye
Author: S. Gillis
Author: Shuning Gai
Author: 
Author: Tony Romeo