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This is a position paper about the therapeutic effects of locally applied free IL-2 in the treatment of cancer. Local therapy: IL-2 therapy of cancer was originally introduced as a systemic therapy. This therapy led to about 20% objective responses. Systemic therapy however was very toxic due to the vascular leakage syndrome. Nevertheless, this treatment was a break-through in cancer immunotherapy and stimulated some interesting questions: Supposing that the mechanism of IL-2 treatment is both proliferation and tumoricidal activity of the tumor infiltrating cells, then locally applied IL-2 should result in a much higher local IL-2 concentration than systemic IL-2 application. Consequently a greater beneficial effect could be expected after local IL-2 application (peritumoral = juxtatumoral, intratumoral, intra-arterial, intracavitary, or intratracheal = inhalation). Free IL-2: Many groups have tried to prepare a more effective IL-2 formulation than free IL-2. Examples are slow release systems, insertion of the IL-2 gene into a tumor cell causing prolonged IL-2 release. However, logistically free IL-2 is much easier to apply; hence we concentrated in this review and in most of our experiments on the use of free IL-2. Local therapy with free IL-2 may be effective against transplanted tumors in experimental animals, and against various spontaneous carcinomas, sarcomas, and melanoma in veterinary and human cancer patients. It may induce rejection of very large, metastasized tumor loads, for instance advanced clinical tumors. The effects of even a single IL-2 application may be impressive. Not each tumor or tumor type is sensitive to local IL-2 application. For instance transplanted EL4 lymphoma or TLX9 lymphoma were not sensitive in our hands. Also the extent of sensitivity differs: In Bovine Ocular Squamous Cell Carcinoma (BOSCC) often a complete regression is obtained, whereas with the Bovine Vulval Papilloma and Carcinoma Complex (BVPCC) mainly stable disease is attained. Analysis of the results of local IL-2 therapy in 288 cases of cancer in human patients shows that there were 27% Complete Regressions (CR), 23% Partial Regressions (PR), 18% Stable Disease (SD), and 32% Progressive Disease (PD). In all tumors analyzed, local IL-2 therapy was more effective than systemic IL-2 treatment. Intratumoral IL-2 applications are more effective than peritumoral application or application at a distant site. Tumor regression induced by intratumoral IL-2 application may be a fast process (requiring about a week) in the case of a highly vascular tumor since IL-2 induces vascular leakage/edema and consequently massive tumor necrosis. The latter then stimulates an immune response. In less vascular tumors or less vascular tumor sites, regression may require 9-20 months; this regression is mainly caused by a cytotoxic leukocyte reaction. Hence the disadvantageous vascular leakage syndrome complicating systemic treatment is however advantageous in local treatment, since local edema may initiate tumor necrosis. Thus the therapeutic effect of local IL-2 treatment is not primarily based on tumor immunity, but tumor immunity seems to be useful as a secondary component of the IL-2 induced local processes. If local IL-2 is combined with surgery, radiotherapy or local chemotherapy the therapeutic effect is usually greater than with either therapy alone. Hence local free IL-2 application can be recommended as an addition to standard treatment protocols. Local treatment with free IL-2 is straightforward and can readily be applied even during surgical interventions. Local IL-2 treatment is usually without serious side effects and besides minor complaints it is generally well supported. Only small quantities of IL-2 are required. Hence the therapy is relatively cheap. A single IL-2 application of 4.5 million U IL-2 costs about 70 Euros. Thus combined local treatment may offer an alternative in those circumstances when more expensive forms of treatment are not available, for instance in resource poor countries.
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http://dx.doi.org/10.1007/s00262-008-0455-z | DOI Listing |
Front Immunol
December 2024
Department of Dermatology, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, United States.
Introduction: Cytokines and chemokines direct the inflammatory response and may serve as markers of immune dysregulation in Pemphigus vulgaris (PV), an autoimmune blistering skin disorder. Previous studies on limited numbers of patients and cytokine profiles in PV have produced equivocal results regarding the role these mediators play in disease.
Methods: In this study, we interrogated serum samples from 116 PV patients and 29 healthy controls by multiplexed bead array assays across a comprehensive set of cytokines and chemokines covering several functional categories, including IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, IL-21, IL-22, IL-23, TNFα, IFNγ, MCP-1, and Eotaxin.
BMC Infect Dis
December 2024
Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, UP, 221005, India.
Background: Lymphatic Filariasis (LF) is a neglected tropical disease affecting more than 882 million people in 44 countries of the world. A multi-epitope prophylactic/therapeutic vaccination targeting filarial defense proteins would be invaluable to achieve the current LF elimination goal.
Method: Two groups of proteins, namely Anti-oxidant (AO) and Heat shock proteins (HSPs), have been implicated in the effective survival of the filarial parasites in their hosts.
Int J Biol Macromol
December 2024
Bio-Convergence Materials R&D Division, Korea Institute of Ceramic Engineering and Technology, 202, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea. Electronic address:
Cancer, a key factor in declining global life expectancy, has driven the integration of chemotherapy and immunotherapy to address multidrug resistance and influence the tumor microenvironment. We developed a novel vaccine delivery carrier, a chitosan-coated polylactic acid/poloxamer nanoparticle (CPP NP), designed to co-encapsulate an anticancer drug and antigen without any chemical conjugation process, enabling effective and synergistic cancer chemo-immunotherapy. The CPP NP achieved synergistic efficacy through paclitaxel (PTX), an immunogenic cell death-inducing chemotherapeutic agent; ovalbumin (OVA), which promotes dendritic cell maturation; and enhanced cellular uptake facilitated by chitosan.
View Article and Find Full Text PDFACS Nano
December 2024
State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
The development of novel detection technology for meat species authenticity is imperative. Here, we developed a machine learning-supported, dual-channel biosensor-in-microdroplet platform for meat species authenticity detection named CC-drop (RISPR/Cas12a digital single-molecule microdroplet biosensor). This strategy allowed us to quickly identify and analyze animal-derived components in foods.
View Article and Find Full Text PDFBiochimie
November 2024
Zhenjiang Hospital of Chinese Traditional and Western Medicine, Affiliated Zhenjiang Integrated Hospital of Traditional Chinese and Western Medicine of Xinglin College, Nantong University, Zhenjiang, 212000, China. Electronic address:
Human thymic stromal lymphopoietin (TSLP) is a pro-inflammatory cytokine located at the top of inflammatory cascade that makes it a promising therapeutic target in allergic asthma. The cell surface receptor of TSLP is a heterodimer consisting of a TSLP receptor (TSLPR) and an interleukin-17 receptor α (IL-7Rα). The TSLPR subunit should be first added to the free TSLP to form a TSLPR/TSLP pre-complex, which further recruits the IL-7Rα subunit to obtain the final TSLPR/IL-7Rα/TSLP complex.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!