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Česká republika Praha
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0032 (0)16 41 44 07
Recombinant Human Interleukin-2 (IL2)
(Cat. No.: C013)
In vitro studies performed on human cell lines demonstrate the immunoregulatory properties of IL-2 including: 1) enhancement of lymphocyte mitogenesis and stimulation of long-term growth of human IL-2 dependent edll lines; 2) enhancement of lymphocyte cytotoxicity; 3) induction of killer cell (lymphokine-activated (LAK) and natural (NK)) activity; 4) dnduction of interferon-gamma production.
Recombinant Human interleukin-2 is a highly purified protein with a molecular weight of approximately 15,300 Daltons. The chemical name is des-alanyl-1, serine-125 human interleukin-2. It is produced by recombinant DNA technology using a genetically engineered E. coli strain containing an analog of the human interleukin-2 gene. Genetic engineering techniques were used to modify the human IL-2 gene, and the resulting expression clone encodes a modified human IL-2. This recombinant form differs from native interleukin-2 in following ways: 1) it is not glycosylated; 2) the molecule has no N-terminal alanine; 3) the molecule has serine substituted for cysteine at amino acid position 125; 4) the aggregation state of molecule is likely to be different from that of native IL-2.
Biological activity: The ED50 as determined by the dose-dependant stimulation of murine CTLL-2 cells is less then 0.1 ng/ml, corresponding to a Specific Activity of 1.0 x 107 IU/ mg.
Purity: Greater than 95% as determined by
(a) Analysis by SEC-HPLC.
(b) Analysis by reducing and non-reducing SDS-PAGE Silver Stained gel.
Isoelectric Point: the main zone between 6.5~7.5 analysis by IEF.
Amino-Acid Sequence: The sequence of the first fifteen N-terminal amino acids was determined and was found to be Met-Ala-Pro-Thr-Ser-Ser-Ser-Thr-Lys-Lys-Thr-Gln-Leu- Gln-Leu-Glu.
Endotoxin: Less than 0.1ng/µg (0.1IEU/µg) determined by LAL test.
Formulation: The protein (1.1mg/ml) was lyophilized after extensive dialysis against 0.17mg sodium monobasic and 0.89mg dibasic sodium phosphate buffer to a pH=7.5.
Storage: Lyophilized rHuIL-2 although stable at room temperature for 3 weeks, should be stored desiccated below -18oC. Upon reconstitution rHuIL-2 should be stored at 4oC between 2-7 days and for future use below -18oC. For long-term storage it is recommended to add a carrier protein (0.1% HSA or BSA).
Please avoid freeze-thaw cycles.
Reconstitution: It is recommended to reconstitute the lyophilized rHuIL-2 in sterile 18MΩ-cm H2O not less than 100µg/ml, which can then be further diluted to other aqueous solutions.
1: Curr HIV Res 2009 Jan;Vol 7(1)
IL-2, IL-7 and IL-15 as Immuno-Modulators During SIV/HIV Vaccination and Treatment.
[Abstract] While highly active antiretroviral therapy (HAART) regimens have proven to be effective in controlling active HIV replication, complete recovery of CD4+ T cells does not always occur, even among patients with high level virologic control. Recent advances in understanding the biology of T cell production and homeostasis have created the potential to augment anti-viral therapies with immunotherapies designed to facilitate recovery of the HIV-damaged immune system, in particular, the recovery of CD4+ T cell populations. The common gamma-chain cytokines IL-2, IL-7 and IL-15 are primary regulators of T cell homeostasis and thus have been considered prime candidate immunotherapeutics, both for increasing T cell levels/function and for augmenting vaccine-elicited
viral-specific T cell responses. Recent studies have established that these cytokines have distinct functional roles in immune homeostasis, which focus on specific T cell populations. The ability of these cytokines to provide immunotherapeutic benefit to HIV+ patients will depend on their ability to stably increase or functionally enhance the desired T cell target population without adverse virologic or clinical consequences.
2: Cytotherapy 2009 Jan;
Modifying interleukin-2 concentrations during culture improves function of T cells for adoptive immunotherapy.
[Abstract] Background Adoptive immunotherapy with cytotoxic T cells has shown promising clinical results in patients with metastatic melanoma and post-transplant-associated viral infections. Cell transfer therapies often require the ex vivo expansion of large numbers of reactive lymphocytes. Therefore interleukin-2 (IL-2), a potent T-cell mitogenic cytokine that critically affects the features and effectiveness of T cells, is frequently added to cell culture media. Methods We examined the influence of various IL-2 concentrations on cell growth, cytotoxicity, cytokine release and surface marker expression of tumor-infiltrating lymphocytes (TIL) during a standard 14-day rapid expansion phase. The study was conducted under good manufacturing practice (GMP) conditions, using
approved reagents in a class 10 000 laboratory. Results T-cell cultures grown in very high IL-2 concentrations (600-6000 IU/mL) expanded massively and maximally secreted interferon (IFN)-gamma in response to antigenic stimulation, but exhibited only low direct cytotoxicity. On the other hand, TIL cultures grown in low concentrations of IL-2 throughout the rapid expansion phase expanded to a lower extent and barely secreted IFN-gamma but displayed high cytotoxic activity. A combined approach of starting with 10-120 IU/mL IL-2 during the first week, followed by increasing the IL-2 concentration to 6000 IU/mL during the second week, results in T cells that expand well, maximally produce IFN-gamma and are highly cytotoxic against tumor cells. Discussion Fine tuning of the IL-2 concentration
during ex vivo expansion of T cells can yield high numbers of T cells with optimal features for clinical use.
3: Med Oncol 2009 Jan;
The application of high-dose interleukin-2 for metastatic renal cell carcinoma.
[Abstract] Renal cell carcinoma (RCC) evokes an immune response, which has occasionally resulted in spontaneous and dramatic remissions [1-3]. In an attempt to reproduce or accentuate this response, various immunotherapeutic strategies have been studied. The most consistent anti-tumor activity has been reported with interferon alfa (IFN-alpha) and interleukin 2 (IL-2). In recent years, randomized trials have suggested that high-dose intravenous bolus IL-2 is superior in terms of response rate and possibly response quality to regimens that involve either low-dose IL-2 and IFN-alpha, intermediate- or low-dose IL-2 alone, or low-dose IFN-alpha alone. As this list of effective therapies for RCC grows, improvements in patient selection will be necessary to ensure that the
only therapy capable of producing durable remissions will remain available to the patients who should receive it [4-7].
4: Med Oncol 2009 Jan;
The biology of interleukin-2 efficacy in the treatment of patients with renal cell carcinoma.
[Abstract] Renal cell carcinoma (RCC) is the eighth most common malignancy in adults in the United States. More than 50% of individuals present with metastatic disease and conventional chemotherapeutic strategies have been associated with poor response rates. Immunotherapy with Interleukin (IL)-2, however, induces durable remission, achieving >10 year recurrence free survival in 5-10% of patients with advanced RCC. First described as a T cell growth factor, IL-2 has a wide spectrum of effects in the immune system. Some of the possible mechanisms by which IL-2 carries out its anticancer effects include the augmentation of cytotoxic immune cell functions and reversal of T cell anergy, enabling delivery of immune cells and possibly serum components into tumor. IL-2
indirectly limits tumor escape mechanisms such as defective tumor cell expression of Class I or Class II molecules or expansion of regulatory T cells. Indirect effects on the tumor microenvironment are also likely and associated with rather dramatic T cell infiltration during the global delayed type hypersensitivity response that is associated with systemic IL-2 administration. The IL-2 signaling pathway, its effects on immune cells, and its role in various independent mechanisms of tumor surveillance likely play a role but little substantive data defining a clear phenotype or genotype of IL-2 responders distinguishing them from nonresponders has emerged in the last 25 years since IL-2 therapy was initiated. At best, we can only speculate that the disturbed homeostatic host/tumor interaction
is reset in a small subset of patients allowing an antitumor response to recover or ensue.
Protein Accession No.:
MAPTS SSTKK TQLQL EHLLL DLQMI LNGIN NYKNP KLTRM LTFKF YMPKK ATELK HLQCL EEELK PLEEV LNLAQ SKNFH LRPRD LISNI NVIVL ELKGS ETTFM CEYAD ETATI VEFLN RWITF SQSII STLT
*NOTE: ALL PRODUCTS ARE FOR RESEARCH USE ONLY