Interleukin 2 (Aldesleukin)
Interleukin 2 (IL-2) is a naturally occurring cytokine made by T-lymphocytes (a type of white blood cell). It stimulates the growth and activity of other T-lymphocytes and B-lymphocytes as part of the immune system. Aldesleukin (Interleukin 2 produced in the laboratory) can be used in the treatment of certain cancers to boost the immune system to help the body fight cancer.
Latest Research Publications
Web Resources: IL2 (6 links)
Latest Research Publications
Treatment Outcome of Low-dose Interleukin-2 Therapy in Patients with Metastatic Renal Cell Carcinoma.
Anticancer Res. 2016; 36(9):4961-4 [PubMed] Related Publications
Immunostimulation by cytosine-phosphate-guanine oligodeoxynucleotides in combination with IL-2 can improve the success rate of karyotype analysis in chronic lymphocytic leukaemia.
Br J Biomed Sci. 2016; 73(3):110-114 [PubMed] Related Publications
MATERIALS AND METHODS: Bone marrow specimens were collected from 36 patients with CLL. CLL cells were cultured with CpG-ODN type DSP30 plus IL-2 for 72 h, following which R-banding analysis was conducted. Conventional culture without the immunostimulant served as the control group. The incidence of genetic abnormalities was measured by fluorescence in situ hybridisation (FISH) using a panel of five specific probes: D13S25 (13q14.3), RB1 (13q14), P53 (17p13), ATM (11q22.3) and CSP12 (trisomy 12, +12).
RESULTS: In the control group, chromosome analysis achieved a success rate of only 22.2, and 11.1% of abnormal karyotypes were detected. After immunostimulation with DSP30 plus IL-2, chromosome analysis achieved a success rate of up to 91.6, and 41.6% of abnormal karyotypes were detected. FISH analysis detected 77.7% of abnormalities. FISH combined with CpG-ODN DSP30 plus IL-2 improved the detection rate of chromosomal abnormalities in CLL to 83.3%.
CONCLUSION: CpG-ODN DSP30 combined with IL-2 is effective in improving the detection rate of chromosomal abnormalities in CLL cells. This combination with FISH analysis is conducive to increasing the detection rate of genetic abnormalities in CLL.
Pleiotropic Effects of IL-2 on Cancer: Its Role in Cervical Cancer.
Mediators Inflamm. 2016; 2016:2849523 [PubMed] Free Access to Full Article Related Publications
Combined therapy with oncolytic adenoviruses encoding TRAIL and IL-12 genes markedly suppressed human hepatocellular carcinoma both in vitro and in an orthotopic transplanted mouse model.
J Exp Clin Cancer Res. 2016; 35:74 [PubMed] Free Access to Full Article Related Publications
METHODS: Herein, we investigated the therapeutic efficacy of concurrent therapy with two armed oncolytic adenoviruses encoding human TRAIL gene (Ad-ΔB/TRAIL) and IL-12 gene (Ad-ΔB/IL-12), respectively, on preclinical models of human HCC, and also elucidated the possible underlying mechanisms. The effects of Ad-ΔB/TRAIL+Ad-ΔB/IL-12 combination therapy were assessed both in vitro on Hep3B and HuH7 human HCC cell lines and in vivo on HCC-orthotopic model established in the livers of athymic nude mice by intrahepatic implantation of human Hep3B cells.
RESULTS: Compared to therapy with non-armed control Ad-ΔB, combined therapy with Ad-ΔB/TRAIL+Ad-ΔB/IL-12 elicited profound anti-HCC killing effects on Hep3B and HuH7 cells and on the transplanted Hep3B-orthotopic model. Efficient viral replication and TRAIL and IL-12 expression were also confirmed in HCC cells and the harvested tumor tissues treated with this combination therapy. Mechanistically, co-therapy with Ad-ΔB/TRAIL+Ad-ΔB/IL-12 exhibited an enhanced effect on apoptosis promotion, activation of caspase-3 and-8, generation of anti-tumor immune response evidenced by upregulation of interferon gamma (IFN-γ) production and infiltration of natural killer-and antigen presenting cells, and remarkable repression of intratumor vascular endothelial growth factor (VEGF) and cluster of differentiation 31 (CD31) expression and tumor microvessel density.
CONCLUSIONS: Overall, our data showed a favorable therapeutic effect of Ad-ΔB/TRAIL+Ad-ΔB/IL-12 combination therapy against human HCC, and may therefore constitute a promising and effective therapeutic strategy for treating human HCC. However, further studies are warranted for its reliable clinical translation.
Breast cancer gene therapy using an adenovirus encoding human IL-2 under control of mammaglobin promoter/enhancer sequences.
Cancer Gene Ther. 2016; 23(6):178-87 [PubMed] Related Publications
Natural killer cells stimulated with PM21 particles expand and biodistribute in vivo: Clinical implications for cancer treatment.
Cytotherapy. 2016; 18(5):653-63 [PubMed] Related Publications
METHODS: We developed a particle-based method that is simple, effective and specifically expands cytotoxic NK cells from peripheral blood mononuclear cells (PBMCs) both ex vivo and in vivo. This method uses particles prepared from plasma membranes of K562-mb21-41BBL cells, expressing 41BBL and membrane bound interleukin-21 (PM21 particles).
RESULTS: Ex vivo, PM21 particles caused specific NK-cell expansion from PBMCs from healthy donors (mean 825-fold, range 163-2216, n = 13 in 14 days) and acute myeloid leukemia patients. The PM21 particles also stimulated in vivo NK cell expansion in NSG mice. Ex vivo pre-activation of PBMCs with PM21 particles (PM21-PBMC) before intraperitoneal (i.p.) injection resulted in 66-fold higher amounts of hNK cells in peripheral blood (PB) of mice compared with unactivated PBMCs on day 12 after injection. In vivo administration of PM21 particles resulted in a dose-dependent increase of PB hNK cells in mice injected i.p. with 2.0 × 10(6) PM21-PBMCs (11% NK cells). Optimal dose of 800 µg/injection of PM21 particles (twice weekly) with low-dose interleukin 2 (1000 U/thrice weekly) resulted in 470 ± 40 hNK/µL and 95 ± 2% of total hCD45(+) cells by day 12 in PB. Furthermore, hNK cells were found in marrow, spleen, lung, liver and brain (day 16 after i.p. PM21/PBMC injection), and mice injected with PM21 particles had higher amounts.
CONCLUSIONS: The extent of NK cells observed in PB, their persistence and the biodistribution would be relevant for cancer treatment.
Dinutuximab: An Anti-GD2 Monoclonal Antibody for High-Risk Neuroblastoma.
Ann Pharmacother. 2016; 50(5):416-22 [PubMed] Related Publications
DATA SOURCES: MEDLINE was searched (1964 to January 2016) using the terms ch14.18, dinutuximab, immunotherapy, and neuroblastoma. Other information was identified from package insert, Biologics License Application, abstracts, news releases, and ClinicalTrials.gov.
STUDY SELECTION AND DATA EXTRACTION: Identified English-language articles were reviewed. Selected studies included phase I through III.
DATA SYNTHESIS: High-risk neuroblastoma is primarily a childhood cancer with 5-year survival rates of 40% to 50%. Treatment for high-risk neuroblastoma includes induction chemotherapy, surgery, myeloablative chemotherapy with autologous hematopoietic stem cell transplant, and radiation therapy. For patients achieving clinical remission, limited treatments exist for preventing relapse. Dinutuximab is a chimeric, human-murine, anti-GD2 monoclonal antibody approved in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), aldesleukin (interleukin-2 [IL-2]), and isotretinoin (13-cis-retinoic acid [RA]) for maintenance treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to first-line multiagent, multimodality therapy. In phase III trials, dinutuximab increased 2-year event-free survival and overall survival when compared to standard treatment. Severe adverse effects of dinutuximab include pain, hypersensitivity reactions, capillary leak syndrome, and hypotension.
CONCLUSIONS: Dinutuximab is the first anti-GD2 monoclonal antibody approved in combination with GM-CSF, IL-2, and RA for maintenance treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to first-line multiagent, multimodality therapy. Ongoing research will determine if dinutuximab could be used earlier in treatment, in nonresponders to initial therapies, in combination with chemotherapy, or in other cancers.
A phase I/IIa clinical trial in stage IV melanoma of an autologous tumor-dendritic cell fusion (dendritoma) vaccine with low dose interleukin-2.
Cancer Immunol Immunother. 2016; 65(4):383-92 [PubMed] Related Publications
METHODS: Autologous tumor lysate and dendritic cells were fused creating dendritoma vaccines for each patient. Phase I patients were vaccinated every 3 months with IL-2 given for 5 days after initial inoculation. Phase IIa patients were vaccinated every 6 weeks with IL-2 given on days 1, 3 and 5 after initial inoculation. Toxicity and clinical outcomes were assessed.
RESULTS: Twenty-five patients were enrolled and inoculated. All dendritoma and IL-2 toxicities were
Durable Response to Treatment With Combination Radiotherapy and High-dose Interleukin-2 in Metastatic Chromophobe Variant Renal Cell Carcinoma.
J Immunother. 2016 Feb-Mar; 39(2):101-3 [PubMed] Related Publications
B7-H3, B7-H4, Foxp3 and IL-2 expression in cervical cancer: Associations with patient outcome and clinical significance.
Oncol Rep. 2016; 35(4):2183-90 [PubMed] Related Publications
NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models.
Clin Cancer Res. 2016; 22(3):680-90 [PubMed] Related Publications
EXPERIMENTAL DESIGN: We evaluated the bioactivity and receptor binding of NKTR-214 and its active IL2 conjugates in vitro; the tumor immunology, tumor pharmacokinetics, and efficacy of NKTR-214 as a single agent and in combination with anti-CTLA-4 antibody in murine tumor models. Tolerability was evaluated in non-human primates.
RESULTS: In a murine melanoma tumor model, the ratio of tumor-killing CD8(+) T cells to Foxp3(+) regulatory T cells was greater than 400 for NKTR-214 compared with 18 for aldesleukin, supporting preferential activation of the IL2 receptor beta over IL2 receptor alpha, due to the location of PEG molecules. NKTR-214 provides a 500-fold greater exposure of the tumor to conjugated IL2 compared with aldesleukin. NKTR-214 showed efficacy as a single agent and provided durable immunity that was resistant to tumor rechallenge in combination with anti-CTLA-4 antibody. NKTR-214 was well tolerated in non-human primates.
CONCLUSIONS: These data support further evaluation of NKTR-214 in humans for a variety of tumor types, adding to the repertoire of potent and potentially curative cancer immunotherapies.
Pharmacokinetics and pharmacodynamics of ch14.18/CHO in relapsed/refractory high-risk neuroblastoma patients treated by long-term infusion in combination with IL-2.
MAbs. 2016; 8(3):604-16 [PubMed] Free Access to Full Article Related Publications
Key genes involved in the immune response are generally not associated with intraprostatic inflammation in men without a prostate cancer diagnosis: Results from the prostate cancer prevention trial.
Prostate. 2016; 76(6):565-74 [PubMed] Article available free on PMC after 01/05/2017 Related Publications
METHODS: Included in this cross-sectional study were 205 white controls from a case-control study nested in the placebo arm of the Prostate Cancer Prevention Trial. We analyzed inflammation data from the review of H&E-stained prostate tissue sections from biopsies performed per protocol at the end of the trial irrespective of clinical indication, and data for 16 SNPs in key genes involved in the immune response (IL1β, IL2, IL4, IL6, IL8, IL10, IL12(p40), IFNG, MSR1, RNASEL, TLR4, TNFA; 7 tagSNPs in IL10). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between carrying at least one minor allele and having at least one biopsy core (of a mean of three reviewed) with inflammation.
RESULTS: None of the SNPs evaluated was statistically significantly associated with having at least one core with inflammation. However, possible inverse associations were present for carrying the minor allele of rs2069762 (G) in IL2 (OR = 0.51, 95%CI 0.25-1.02); carrying two copies of the minor allele of rs1800871 (T) of IL10 (OR = 0.29, 95%CI 0.08-1.00); and carrying the minor allele of rs486907 (A) in RNASEL (OR = 0.52, 95%CI 0.26-1.06). After creating a genetic risk score from the three SNPs possibly associated with inflammation, the odds of inflammation increased with increasing number of risk alleles (P-trend = 0.008).
CONCLUSION: While our findings do not generally support a cross-sectional link between individual SNPs in key genes involved in the immune response and intraprostatic inflammation in men without a prostate cancer diagnosis, they do suggest that some of these variants when in combination may be associated with intraprostatic inflammation in benign tissue.
Effects of flurbiprofen axetil on postoperative serum IL-2 and IL-6 levels in patients with colorectal cancer.
Genet Mol Res. 2015; 14(4):16469-75 [PubMed] Related Publications
Adjuvant Ovarian Suppression, High-dose Chemotherapy and Immunotherapy for Premenopausal Patients with High-risk Breast Cancer.
Anticancer Res. 2015; 35(12):6847-53 [PubMed] Related Publications
PATIENTS AND METHODS: Forty-two BC>10 received, in sequence, the following adjuvant treatments: luteinizing hormone releasing hormone (LH-RH) analog for 5 years; anthracycline-based induction chemotherapy; radiation therapy; platinum-based high-dose CT, with autologous bone marrow transplantation; immunotherapy with interleukin 2 (IL2) and 13-cis retinoic acid (RA); anastrazole given 5 years to estrogen receptor-positive patients. Primary endpoints of the study were disease-free survival (DFS) and overall (OS) survival. A secondary endpoint was toxicity.
RESULTS: The median age of patients was 41 years, and the mean number of positive axillary nodes was 14. Estrogen and progesterone receptors were positive in 57% and 29% of patients respectively, while 14% of patients had triple-negative disease. With a median follow-up of 120 months for patients remaining alive at the end of study, median DFS and OS, had not yet been reached. The 20-year DFS and OS rates were 63.8%, and 81.6%, respectively. One to two years after the end of the therapy, three patients had had four full-term pregnancies.
CONCLUSION: Treatment with LH-RH analog, high-dose CT, peripheral blood progenitor cells and IL2 with RA for patients with BC>10 is feasible, has moderate toxicity, while preserving ovarian function, seems to improve the expected DFS and OS for these high-risk patients.
Clinical significance of IL-2 and IL-10 gene polymorphisms and serum levels in patients with basal-cell carcinoma.
Biomark Med. 2016; 10(2):185-95 [PubMed] Related Publications
RESULTS: The presence of the IL-2 -330 GG genotype or IL-10 -1082 GA increased the risk of BCC (OR 3.68) (OR 3.07). IL-10 -1082 AA or GA and IL-2 -330 GG genotype increased the risk of BCC (OR 9.63). IL-2 serum levels were significantly lower (p < 0.0004) in BCC patients while IL-10 concentration was significantly higher (p < 0.00001).
CONCLUSION: The polymorphisms in IL-2 and IL-10 genes may contribute to BCC susceptibility and influence the clinical course of BCC in polish population.
HLA class I downregulation is associated with enhanced NK-cell killing of melanoma cells with acquired drug resistance to BRAF inhibitors.
Eur J Immunol. 2016; 46(2):409-19 [PubMed] Article available free on PMC after 01/05/2017 Related Publications
NK cell expression of natural cytotoxicity receptors may determine relapse risk in older AML patients undergoing immunotherapy for remission maintenance.
Oncotarget. 2015; 6(40):42569-74 [PubMed] Article available free on PMC after 01/05/2017 Related Publications
Interleukin-2 as maintenance therapy for children and adults with acute myeloid leukaemia in first complete remission.
Cochrane Database Syst Rev. 2015; (11):CD010248 [PubMed] Related Publications
OBJECTIVES: To evaluate the efficacy and safety of IL-2 as maintenance therapy for children and adults with AML who have achieved first CR and have not relapsed.
SEARCH METHODS: We systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 8), MEDLINE (1950 to August 2015), EMBASE (1950 to August 2015), LILACS (1982 to August 2015), CBM (1978 to August 2015), relevant conference proceedings (2000 to 2015), and metaRegister of Controlled Trials (since inception to August 2015) of ongoing and unpublished trials. In addition, we screened the reference lists of relevant trials and reviews.
SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCTs) comparing IL-2 with no treatment in people with AML who had achieved first CR and had not relapsed. We did not identify studies comparing IL-2 versus best supportive care or maintenance chemotherapy or studies comparing IL-2 plus maintenance chemotherapy versus maintenance chemotherapy alone.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies, extracted data with a predefined extraction form, and assessed risk of bias of included studies. We extracted data on the following outcomes: disease-free survival, overall survival, event-free survival, treatment-related mortality, adverse events, and quality of life. We measured the treatment effect on time-to-event outcomes and dichotomous outcomes with hazard ratio (HR) and risk ratio, respectively. We used inverse-variance method to combine HRs with fixed-effect model unless there was significant between-study heterogeneity.
MAIN RESULTS: We included nine RCTs with a total of 1665 participants, comparing IL-2 with no treatment. Six studies included adult participants, and three studies included both adults and children. However, the latter three studies did not report data for children, thus we were unable to conduct subgroup analysis of children. One Chinese study did not report any outcomes of interest for this review. We included six trials involving 1426 participants in the meta-analysis on disease-free survival, and included five trials involving 1355 participants in the meta-analysis on overall survival. There is no evidence for difference between IL-2 group and no-treatment group regarding disease-free survival (HR 0.95; 95% CI 0.86 to 1.06, P = 0.37; quality of evidence: low) or overall survival (HR 1.05; 95% CI 0.95 to 1.16, P = 0.35; quality of evidence: moderate). Based on one trial of 161 participants, IL-2 exerted no effect on event-free survival (HR 1.02; 95% CI 0.79 to 1.32, P = 0.88; quality of evidence: low). Adverse events (including thrombocytopenia, neutropenia, malaise/fatigue, and infection/fever) were more frequent in participants receiving IL-2, according to one trial of 308 participants. No mortality due to adverse events was reported. None of the included studies reported treatment-related mortality or quality of life.
AUTHORS' CONCLUSIONS: There is no evidence for a difference between IL-2 maintenance therapy and no treatment with respect to disease-free survival or overall survival of people with AML in first CR; however, the quality of the evidence is moderate or low, and further research is likely or very likely to have an important impact on the estimate or our confidence in the estimate. Adverse events seem to be more frequent in participants treated with IL-2, but the quality of the evidence is very low and our confidence in the estimates is very uncertain. Thus, further prospective randomised trials are needed before definitive conclusions can be drawn on these issues.
Enhancing Dendritic Cell-based Immunotherapy with IL-2/Monoclonal Antibody Complexes for Control of Established Tumors.
J Immunol. 2015; 195(9):4537-44 [PubMed] Article available free on PMC after 01/05/2017 Related Publications
Selective targeting of JAK/STAT signaling is potentiated by Bcl-xL blockade in IL-2-dependent adult T-cell leukemia.
Proc Natl Acad Sci U S A. 2015; 112(40):12480-5 [PubMed] Article available free on PMC after 01/05/2017 Related Publications
Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia: Clinical and biologic correlations.
Genes Chromosomes Cancer. 2015; 54(12):818-26 [PubMed] Related Publications
100% Complete response rate in patients with cutaneous metastatic melanoma treated with intralesional interleukin (IL)-2, imiquimod, and topical retinoid combination therapy: results of a case series.
J Am Acad Dermatol. 2015; 73(4):645-54 [PubMed] Related Publications
OBJECTIVE: We sought to evaluate the effectiveness of intralesional IL-2 combined with topical imiquimod and retinoid for treatment of cutaneous metastatic melanoma.
METHODS: A retrospective case series of 11 patients with cutaneous metastatic melanoma were treated with intralesional IL-2 combined with topical imiquimod and retinoid.
RESULTS: A 100% complete local response rate with long-term follow-up (average of 24 months) was seen in all 11 patients treated with this proposed regimen. Biopsy specimens of treated sites confirmed absence of malignant cells. The most common treatment-related adverse event was rigors.
LIMITATIONS: Small number of patients, retrospective review of charts, and lack of a comparison group were limitations.
CONCLUSION: Intralesional IL-2 administered concomitantly with topical imiquimod and a retinoid cream is a promising therapeutic option for managing cutaneous melanoma metastases. The regimen was well tolerated and should be considered as a reasonable alternative to surgical excision.
Contemporary trends in high-dose interleukin-2 use for metastatic renal cell carcinoma in the United States.
Urol Oncol. 2015; 33(11):496.e11-6 [PubMed] Article available free on PMC after 01/05/2017 Related Publications
METHODS: Our cohort comprised a weighted estimate of all patients undergoing HD IL-2 treatment for mRCC from 2004 to 2012 using the Premier Hospital Database. We assessed temporal trends in HD IL-2 use including patient, disease, and hospital characteristics stratified by era (pre-TT uptake: 2004-2006, uptake: 2007-2009, and post-TT uptake: 2010-2012) and fitted multivariable regression models to identify predictors of treatment toxicity and tolerability.
RESULTS: An estimated 2,351 patients received HD IL-2 therapy for mRCC in the United States from 2004 to 2012. The use decreased from 2004 to 2008. HD IL-2 therapy became increasingly centralized in teaching hospitals (24% of treatments in 2004 and 89.5% in 2012). Most patients who received HD IL-2 therapy were men, white, younger than 60 years, had lung metastases, and were otherwise healthy. Vasopressors, intensive care unit admission, and hemodialysis were necessary in 53.4%, 33.0%, and 7.1%, respectively. Factors associated with toxicities in multivariable analyses included being unmarried, male sex, and multiple metastatic sites. African Americans and patients with single-site metastases were less likely to receive multiple treatment cycles.
CONCLUSIONS: HD IL-2 therapy is used infrequently for mRCC in the United States, and its application has diminished with the uptake of TT. Patients are being increasingly treated in teaching hospitals, suggesting a centralization of care and possible barriers to access. A recent slight increase in HD IL-2 therapy use likely reflects recognition of the inability of TT to effect a complete response.
Effect of targeted ovarian cancer therapy using amniotic fluid mesenchymal stem cells transfected with enhanced green fluorescent protein-human interleukin-2 in vivo.
Mol Med Rep. 2015; 12(4):4859-66 [PubMed] Article available free on PMC after 01/05/2017 Related Publications
Interleukin 2 as a potential cancer marker in patients after kidney transplantation.
Ann Agric Environ Med. 2015; 22(2):320-4 [PubMed] Related Publications
MATERIALS AND METHODS: A group of 74 (43M and 31F; aged 46.8 ± 12 years) kidney transplant recipients was investigated in a three-year follow-up study. During the time of observation, 7 patients were diagnosed with neoplasm (7.4 ± 1.5 years after transplantation). A serum level of IL2 (ELISA test) and mRNA level of IL1beta, IL10 and TNFalfa in peripheral mononuclear blood cells - PBMCs (QRT - PCR method) were measured in every year of observation. Analysis of variances and t-Student test were used in groups mean comparison: N - patients developing malignant neoplasm group (24 probes); M - set of probes from patients with malignancies at the moment of diagnosis (11 probes); P - set of probes from patients before developing malignant neoplasm (10 probes); C - control group of healthy transplant recipients (31 probes).
RESULTS: Among the analyzed agents, only serum IL2 level differed between the analyzed groups, with higher values in the M compared with the P group (p<0.05) and with C group (p<0.01). There were no differences neither between N and C or P and C groups (p = 0.98), nor any correlation between IL2 and IL1b, IL2 and TNFalfa.
CONCLUSIONS: The results may indicate that IL2 serum level might be consider as a useful late unspecific cancer marker, although larger studies should yield verification of this finding.
Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer.
Mol Cell Biochem. 2015; 407(1-2):281-7 [PubMed] Related Publications
Evaluation of IL-2, IL-6, IL-8 and IL-10 in Malignant Melanoma Diagnostics.
Anticancer Res. 2015; 35(6):3537-41 [PubMed] Related Publications
PATIENTS AND METHODS: A group of 236 persons was assessed: 175 patients with melanomas and 61 healthy persons. Melanoma patients were divided to four groups according to Breslow score. We determined IL-2, IL-6, IL-8 and IL-10 in each plasma sample. Interleukin plasma levels were assayed using a Human Cytokine Milliplex Map kit. Measurements were performed using the Bio-Plex MAGPIX Multiplex Reader. Plasma samples were collected prior to surgery or any other form of treatment. All melanoma diagnoses were histologically verified.
RESULTS: We compared interleukin plasma levels in the healthy group and plasma levels in each Breslow score stage. In the first Breslow score stage, IL-2 (p<0.0001), IL-6 (p=0.0004) and IL-10 (p<0.0001) were positive. In the second Breslow score, stage IL-2 (p<0.0001), IL-6 (p<0.0001), IL-8 (p=0.0017) and IL-10 (p<0.0001) were positive. By comparing the group of positive and negative sentinel node metastasis, we observed a statistically significant difference in two interleukins: The median of IL-2 levels in the negative group was 5.88 pg/ml compared to 32.57 pg/ml in the positive group (p=0.0005). The median of IL-6 levels in the negative group was 4.80 pg/ml compared to 32.02 pg/ml in the positive group (p=0.0048).
CONCLUSION: Interleukins IL-2, IL-6 and IL-10 are promising biomarkers of early-stage melanoma. IL-2 and IL-6 appear to be prognostic biomarkers.
Effective Treatment of Transmissible Venereal Tumors in Dogs with Vincristine and IL2.
Anticancer Res. 2015; 35(6):3385-91 [PubMed] Related Publications
PATIENTS AND METHODS: We treated 12 dogs with TVT with 1-4 intratumoral treatments with vincristine and IL-2. Per treatment we used vincristine (0.5-0.7 mg/m(2)) and IL2 (2×10(6) units). The injections were given at weekly intervals.
RESULTS: Early therapeutic effects were: three complete regressions, four partial regressions, three stable disease, and two progressive disease. Late therapeutic effects were established 45-60 months after the first presentation; there were five complete regressions, no partial regressions, nor stable or progressive diseases. Interestingly, all five dogs with late therapeutic effects were in good health. No tumor recurrence was noted.
CONCLUSION: Intratumoral treatment of TVT with vincristine and IL2 appears to have impressive therapeutic effects.
A combination of YM-155, a small molecule survivin inhibitor, and IL-2 potently suppresses renal cell carcinoma in murine model.
Oncotarget. 2015; 6(25):21137-47 [PubMed] Article available free on PMC after 01/05/2017 Related Publications