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[Antitumor effects of cytokines with immunomodulatory activity]
C Radzikowski1, E Pajtasz-Piasecka, H Glazman-Kuśnierczyk
1Zakład Immunologii Nowotworów, Instytut Immunologii i Terapii Doświadczalnej im. Ludwika Hirszfelda, PAN, Wrocław.
Abstract:
The attempts to augment the immune responses in patients with solid tumors have been undertaken since long time ago. Recognition of the nature and biologic functions of cytokines and their receptors was the turning point in the studies on potential use of various immunotherapeutics. The availability of genetically engineered recombinant preparations enabled conducting basic and applied studies on a wide scale. There are numerous Phase I and II clinical trials ongoing in patients with melanoma, renal cell carcinoma, bronchogenic and digestive tract cancers, leukemias as well as other malignancies. Several cytokine preparations were shown to be quite toxic upon systemic application; at present they are more frequently used in loco regional (peritumoral) administration. More recently, a variety of tumor cells or tumor infiltrating lymphocytes (TIL) have been genetically engineered by transfection with different cytokine genes to yield "autovaccines". When applied locally they can be the source of cytokines, which in turn might be beneficial for the organism by unsettling the tumor-host balance. Cytokines are used in mono- and multidrug therapy in combinations with other cytokine or cytostatics. The colony-forming stimulating factors that stimulate proliferation of hematopoietic cells and induce their differentiation have found their application (e.g. GM-CSF or G-CSF) in enhancing the bone marrow renewal after chemo- and radiotherapy in cancer patients. They are also applied after bone marrow transplantation in patients with myelogenous leukemias. The results of immunotherapeutic approaches in cancer treatment are far from expected. Nevertheless, they gave us the fundamental insight into the complexity of tumor-host relationship.
Insights
Immunotherapy using cytokines aims to boost immune responses against solid tumors. While systemic cytokine therapy shows toxicity, local administration and engineered "autovaccines" offer promising avenues for cancer treatment.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Context:
- Augmenting immune responses in solid tumors has been a long-standing goal in cancer research.
- Understanding cytokine biology and receptors revolutionized immunotherapeutic strategies.
- Genetically engineered cytokine preparations facilitate extensive basic and applied studies.
Purpose:
- To explore the use of cytokines and engineered autovaccines for cancer immunotherapy.
- To evaluate the efficacy and safety of cytokine-based therapies in various malignancies.
- To investigate novel administration routes like loco-regional delivery for improved therapeutic outcomes.
Summary:
- Numerous clinical trials are investigating cytokine therapies for melanoma, renal cell carcinoma, lung, digestive tract cancers, and leukemias.
- Systemic cytokine administration can be toxic, leading to increased use of loco-regional (peritumoral) delivery and genetically engineered "autovaccines".
- Cytokines are used in monotherapy and combination treatments, including with cytostatics, and colony-stimulating factors (e.g., GM-CSF, G-CSF) aid bone marrow recovery post-treatment.
Impact:
- Cytokine-based immunotherapies have provided fundamental insights into tumor-host interactions, despite results not meeting all expectations.
- Local administration and autovaccine strategies represent evolving approaches to enhance anti-tumor immunity.
- Further research into cytokine mechanisms and delivery is crucial for optimizing cancer treatment outcomes.