Interleukin-2: Clinical applications

Atkins, Michael B.

doi:10.1053/sonc.2002.33077

Cited by 156Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesCutaneous Melanoma Detection and Management

Interleukin-2: Clinical applications

Atkins, Michael B.·2002·Seminars in Oncology

DOI 10.1053/sonc.2002.33077

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Abstract

Interleukin-2 (IL-2) is a promising immunotherapeutic agent for the treatment of metastatic melanoma, acute myelogenous leukemia, and metastatic renal cell carcinoma. While high-dose IL-2 regimens have shown clinical benefit in the treatment of melanoma and renal cell carcinoma, serious dose-limiting toxicities have limited their clinical use in a broader group of patients. Low-dose IL-2 therapy has produced disappointing clinical response rates in melanoma. While the response rates to low-dose IL-2 have been better in renal cell carcinoma, the quality of these responses relative to those seen with high-dose IL-2 therapy remains a concern. The addition of IL-2 to chemotherapeutic regimens (biochemotherapy) has been associated with overall response rates of up to 60% in patients with metastatic melanoma, but this has yet to be translated into a confirmed improvement in survival. It remains to be determined whether further modifications of IL-2-based regimens or the addition of newer agents to IL-2 will produce better tumor response and survival.

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The administration of recombinant cytokines (e.g., interleukin-1, interleukin-6, interleukin-12, interleukin-18, tumor necrosis factor, and interferon-γ) in animal models and for cancer treatment in humans induces severe toxic effects or lethality consistent with the central role of cytokines as mediators of hyperinflammation in cytokine storm.
“The administration of recombinant cytokines (e.g., interleukin-1, interleukin-6, interleukin-12, interleukin-18, tumor necrosis factor [TNF], and interferon-γ) in animal models and for cancer treatment in humans induces severe toxic effects or lethality consistent with the central role of cytokines as mediators of hyperinflammation in cytokine storm.”
From Cytokine storm (2020) · cites this paper as [29]

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Cytoreductive surgery prior to interleukin-2-based therapy in patients with metastatic renal cell carcinoma
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LACK OF RETROPERITONEAL LYMPHADENOPATHY PREDICTS SURVIVAL OF PATIENTS WITH METASTATIC RENAL CELL CARCINOMA
Vasselli, J. R., Yang, J. C., Linehan, W. M., White, D. E., Rosenberg, S. A., & Walther, M. M. (2001) · The Journal of Urology · doi:10.1016/s0022-5347(05)66078-8 · Cited by 165 · see citing works
CD4+CD25+Regulatory T Cells and Their Therapeutic Potential
Randolph, D. A., & Fathman, C. G. (2005) · Annual Review of Medicine · doi:10.1146/annurev.med.57.121304.131337 · Cited by 122 · see citing works
Naturally Occurring Canine Melanoma as a Predictive Comparative Oncology Model for Human Mucosal and Other Triple Wild-Type Melanomas
Hernandez, B., Adissu, H. A., Wei, B., Michael, H., Merlino, G. T., & Simpson, R. M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020394 · Cited by 121 · see citing works
“Due to the durable responses, this cytokine has been licensed for treatment of advanced stage human melanoma in many countries [107].”
Background
A randomised, phase II study of intetumumab, an anti-αv-integrin mAb, alone and with dacarbazine in stage IV melanoma
on the behalf of the CNTO 95 Investigators, O'Day, S. J., Pavlick, A. C., Loquai, C., Lawson, D. H., Gutzmer, R., Richards, J. M., Schadendorf, D., Thompson, J. A., Gonzalez, R. C., et al. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.183 · Cited by 120 · see citing works
IL‐2 induces in vivo suppression by CD4+CD25+Foxp3+ regulatory T cells
Brandenburg, S., Takahashi, T., Rosa, M. D. L., Janke, M., Karsten, G., Muzzulini, T., Orinska, Z., Bulfone-Paus, S., & Scheffold, A. (2008) · European Journal of Immunology · doi:10.1002/eji.200737791 · Cited by 127 · see citing works
Fueling Cancer Immunotherapy With Common Gamma Chain Cytokines
Dwyer, C. J., Knochelmann, H. M., Smith, A. S., Wyatt, M. M., Rivera, G. O. R., Arhontoulis, D. C., Bartee, E., Li, Z., Rubinstein, M. P., & Paulos, C. M. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00263 · Cited by 106 · see citing works
Comparison of the efficacy, safety, and pharmacokinetics of controlled release and immediate release metoclopramide for the management of chronic nausea in patients with advanced cancer
Bruera, E. D., MacEachern, T., Spachynski, K., LeGatt, D. F., MacDonald, R. N., Babul, N., Harsanyi, Z., & Darke, A. C. (1994) · Cancer · doi:10.1002/1097-0142(19941215)74:12 · Cited by 66 · see citing works
CD25+ Regulatory T Cell Depletion Augments Immunotherapy of Micrometastases by an IL-21-Secreting Cellular Vaccine
Comes, A., Rosso, O., Orengo, A. M., Carlo, E. D., Sorrentino, C., Meazza, R., Piazza, T., Valzasina, B., Nanni, P., Colombo, M. P., et al. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.3.1750 · Cited by 105 · see citing works
IL-2/CD25: A Long-Acting Fusion Protein That Promotes Immune Tolerance by Selectively Targeting the IL-2 Receptor on Regulatory T Cells
Ward, N. C., Yu, A., Moro, A., Ban, Y. J., Chen, X., Hsiung, S., Keegan, J., Arbanas, J. M., Loubeau, M., Thankappan, A., et al. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1800907 · Cited by 103 · see citing works
“The poor efficacy of high-dose IL-2 in these settings is due in part to the accompanying expansion of Tregs (15, 16).”
Background
Dynamic changes of specific T cell responses to melanoma correlate with IL-2 administration
Andersen, M. H., Gehl, J., Hadrup, S. R., Pedersen, L. Ø., Becker, J. C., Geertsen, P. F., & Straten, P. T. (2003) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2003.09.009 · Cited by 80 · see citing works
Phase II trial of Modified Vaccinia Ankara (MVA) virus expressing 5T4 and high dose Interleukin-2 (IL-2) in patients with metastatic renal cell carcinoma
Kaufman, H. L., Taback, B., Sherman, W. H., Kim, D. W., Shingler, W. H., Moroziewicz, D. N., DeRaffele, G., Mitcham, J., Carroll, M. W., Harrop, R., et al. (2009) · Journal of Translational Medicine · doi:10.1186/1479-5876-7-2 · Cited by 75 · see citing works
“High-dose bolus interleukin-2 (IL-2) is associated with a consistent and durable objective response in 17% of patients with metastatic RCC and a 6–9% complete response rate [1-3].”
Rational combinations of immunotherapeutics that target discrete pathways
Spranger, S., & Gajewski, T. F. (2013) · Journal for ImmunoTherapy of Cancer · doi:10.1186/2051-1426-1-16 · Cited by 74 · see citing works
“The first cytokine FDA-approved for this purpose is IL-2, for the treatment of patients with metastatic melanoma and kidney cancer [37], although the mechanism of action of this agent in patients has never been firmly established.”
Background
CTLA-4 blockade and the renaissance of cancer immunotherapy
D, S. M. M., & Nitti, D. (2013) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2013.05.003 · Cited by 71 · see citing works
Interleukin 15 Provides Relief to CTLs from Regulatory T Cell–Mediated Inhibition: Implications for Adoptive T Cell–Based Therapies for Lymphoma
Perna, S. K., Angelis, B. D., Pagliara, D., Hasan, S. T., Zhang, L., Mahendravada, A., Heslop, H. E., Brenner, M. K., Rooney, C. M., Dotti, G., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2143 · Cited by 71 · see citing works
“The toxicity associated with the systemic administration of g-chain cytokines, used to support the in vivo persistence of adoptively transferred tumor-specific CTLs (12, 13), and the effects that these cytokines exert on the host inhibitory Tregs (14–17) remain obstacles to improve the clinical”
Background
Local IL-21 Promotes the Therapeutic Activity of Effector T cells by Decreasing Regulatory T Cells Within the Tumor Microenvironment
Kim‐Schulze, S., Kim, H. S., Fan, Q., Kim, D. W., & Kaufman, H. L. (2008) · Molecular Therapy · doi:10.1038/mt.2008.249 · Cited by 66 · see citing works
IL‐21: roles in immunopathology and cancer therapy
Søndergaard, H., & Skak, K. (2009) · Tissue Antigens · doi:10.1111/j.1399-0039.2009.01382.x · Cited by 63 · see citing works
“vascular leak syndrome, requiring intensive care (52).”
Fine-tuned long-acting interleukin-2 superkine potentiates durable immune responses in mice and non-human primate
Merchant, R., Galligan, C. L., Munegowda, M. A., Pearce, L. B., Lloyd, P. M., Smith, P., Merchant, F., & To, M. D. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-003155 · Cited by 59 · see citing works
A new strategy for glycoprotein synthesis: ligation of synthetic glycopeptides with truncated proteins expressed in E. coli as TEV protease cleavable fusion protein
Tolbert, T. J., Franke, D., & Wong, C. (2004) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2004.06.047 · Cited by 55 · see citing works
All- trans Retinoic Acid Stimulates IL-2-Mediated Proliferation of Human T Lymphocytes: Early Induction of Cyclin D3
Engedal, N., Gjevik, T., Blomhoff, R., & Blomhoff, H. K. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.5.2851 · Cited by 53 · see citing works
“IL-2 is a promising therapeutic agent for the treatment of HIV/AIDS (68) and several types of cancers (69).”
Successful Treatment of TAFRO Syndrome, a Variant of Multicentric Castleman’s Disease, with Cyclosporine A: Possible Pathogenetic Contribution of Interleukin-2
Konishi, Y., Takahashi, S., Nishi, K., Sakamaki, T., Mitani, S., Kaneko, H., Mizutani, C., Ukyo, N., Hirata, H., & Tsudo, M. (2015) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.236.289 · Cited by 50 · see citing works
“Moreover, in support of this hypothesis, IL-2 administration is known to induce capillary leak syndrome, elevated creatinine levels, and thrombocytopenia in some cases when used to treat cancer (Atkins et al. 1999; Atkins 2002; Petrella et al. 2007).”
Background
Hybrid Cell Vaccination in Metastatic Melanoma
Haenssle, H. A., Krause, S. W., Emmert, S., Zutt, M., Kretschmer, L., Schmidberger, H., Andreesen, R., & Soruri, A. (2004) · Journal of Immunotherapy · doi:10.1097/00002371-200403000-00008 · Cited by 50 · see citing works
“IL-2 is a potent stimulator of lymphocyte proliferation and has been shown to augment the activity of CTL either alone(44) or in combination with other cytokines.(45,46) The systemic administration of IL-2 in vivo also has a broad range of immunologic effects, including the induction of specific T helper cells, and na…”
Background
Interleukin‐21 ( IL ‐21) synergizes with IL ‐2 to enhance T ‐cell receptor‐induced human T‐cell proliferation and counteracts IL ‐2/transforming growth factor‐β‐induced regulatory T‐cell development
Battaglia, A., Buzzonetti, A., Baranello, C., Fanelli, M., Fossati, M., Catzola, V., Scambia, G., & Fattorossi, A. (2012) · Immunology · doi:10.1111/imm.12061 · Cited by 48 · see citing works
The monoclonal antibody to cytotoxic T lymphocyte antigen 4, ipilimumab, in the treatment of melanoma
Verschraegen, C. F. (2012) · Cancer Management and Research · doi:10.2147/cmar.s15551 · Cited by 46 · see citing works
“Chemotherapy has been widely used to treat patients with unresectable disease, but most of the time the disease fails to respond.(4) Non-specific immunotherapy has induced durable responses in very few patients.”
Rationale for Combining Immunotherapy with Chemotherapy
Dalgleish, A. G. (2015) · Immunotherapy · doi:10.2217/imt.14.111 · Cited by 46 · see citing works
“51 Atkins MB. Interleukin2: clinical applications. Semin. Oncol. 29, 12–17 (2002).”
Renin-angiotensin system (RAS) blockade attenuates growth and metastatic potential of renal cell carcinoma in mice
Araújo, W. F., Naves, M. A., Ravanini, J. N., Schor, N., & Teixeira, V. P. C. (2015) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2014.11.022 · Cited by 45 · see citing works
Role of Cytokines
Khan, M. M. (2008) · Springer eBooks · doi:10.1007/978-0-387-77976-8_2 · Cited by 45 · see citing works
Increase of Circulating CD4+CD25highFoxp3+ Regulatory T Cells in Patients With Metastatic Renal Cell Carcinoma During Treatment With Dendritic Cell Vaccination and Low-Dose Interleukin-2
Berntsen, A., Brimnes, M. K., Straten, P. T., & Svane, I. M. (2010) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3181cd870f · Cited by 42 · see citing works
“Recombinant IL-2 induces durable clinical response in a subset of patients with malignant melanoma and RCC, suggesting that IL-2 therapy predominantly induces immune activation.(23) However, IL-2 signaling is also essential for peripheral expansion and suppressive activity of Treg cells and recent studies have reporte…”
Background
Synergistic Antitumor Response of Interleukin 2 with Melphalan in Isolated Limb Perfusion in Soft Tissue Sarcoma–Bearing Rats
Hoving, S., Brunstein, F., de Wiel‐Ambagtsheer, G. A., van Tiel, S. T., Boeck, G. D., de Bruijn, E. A., Eggermont, A. M. M., & ten Hagen, T. L. M. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-2214 · Cited by 41 · see citing works
“Systemic IL-2 administration is often complicated by significant capillary leakage, with consequent extravasation of interstitial fluid and plasma proteins (14, 15, 26).”
Background
Tumor necrosis factor‐mediated interactions between inflammatory response and tumor vascular bed
ten Hagen, T. L. M., Seynhaeve, A. L. B., & Eggermont, A. M. M. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00619.x · Cited by 40 · see citing works
“In different animal models, IL-2 has been shown to have anti-tumor activity as a single agent (135, 136).”
Background
IL-15: targeting CD8+ T cells for immunotherapy
Diab, A. K., Cohen, A. D., Alpdoğan, Ö., & Perales, M.-A. (2005) · Cytotherapy · doi:10.1016/s1465-3249(05)70786-6 · Cited by 40 · see citing works
Cytokines as clinical adjuvants: how far are we?
Villinger, F. J. (2003) · Expert Review of Vaccines · doi:10.1586/14760584.2.2.317 · Cited by 39 · see citing works
Combination of YM155, a Survivin Suppressant, with Bendamustine and Rituximab: A New Combination Therapy to Treat Relapsed/Refractory Diffuse Large B-cell Lymphoma
Kaneko, N., Mitsuoka, K., Amino, N., Yamanaka, K., Kita, A., Mori, M., Miyoshi, S., & Kuromitsu, S. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2707 · Cited by 38 · see citing works
Overlapping human leukocyte antigen class I/II binding peptide vaccine for the treatment of patients with stage IV melanoma
Celis, E. (2007) · Cancer · doi:10.1002/cncr.22744 · Cited by 38 · see citing works
Targeting the Lung: Preclinical and Comparative Evaluation of Anticancer Aerosols in Dogs with Naturally Occurring Cancers
Khanna, C., & Vail, D. M. (2003) · Current Cancer Drug Targets · doi:10.2174/1568009033481903 · Cited by 36 · see citing works
Antibody-Cytokine Fusion Proteins: Harnessing the Combined Power of Cytokines and Antibodies for Cancer Therapy
Helguera, G. F., Morrison, S. L., & Penichet, M. L. (2002) · Clinical Immunology · doi:10.1006/clim.2002.5302 · Cited by 34 · see citing works
The critical impacts of cytokine storms in respiratory disorders
Tramboo, S. R., Elkhalifa, A. M. E., Khursheed, S. Q., Ali, S. I., Shah, N. N., Taifa, S., Rakhshan, R., Shah, I. H., Mir, M. A., Malik, M., et al. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e29769 · Cited by 31 · see citing works
“Chloroquine phosphate has also been utilized in China to treat adults aged 18 to 65 infected with COVID-19 [98].”
BackgroundMethod
Modifying interleukin-2 concentrations during culture improves function of T cells for adoptive immunotherapy
Besser, M. J., Schallmach, E., Oved, K., Treves, A. J., Markel, G., Reiter, Y., & Schachter, J. (2009) · Cytotherapy · doi:10.1080/14653240802590391 · Cited by 33 · see citing works
Cytokine gene-modified vaccines in the therapy of cancer
Bubenik, J. (1996) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(95)02016-0 · Cited by 33 · see citing works
Randomized trial of dacarbazine versus bleomycin, vincristine, lomustine and dacarbazine (BOLD) chemotherapy combined with natural or recombinant interferon-?? in patients with advanced melanoma
Vuoristo, M., Hahka‐Kemppinen, M., Parvinen, L.-M., Pyrhönen, S. O., Sepp, H., Korpela, M., & Kellokumpu‐Lehtinen, P. (2005) · Melanoma Research · doi:10.1097/00008390-200508000-00010 · Cited by 33 · see citing works
Protection against HPV-16–Associated Tumors Requires the Activation of CD8+ Effector Memory T Cells and the Control of Myeloid-Derived Suppressor Cells
Diniz, M. O., Sales, N. S., Silva, J. R., & Ferreira, L. C. D. S. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0742 · Cited by 32 · see citing works
High-dose interleukin-2: is it still indicated for melanoma and RCC in an era of targeted therapies?
Amin, A., & White, R. L. (2013) · PubMed · Cited by 30 · see citing works
Cytokine Therapy for Cancer
Kim‐Schulze, S., Taback, B., & Kaufman, H. L. (2007) · Surgical Oncology Clinics of North America · doi:10.1016/j.soc.2007.07.011 · Cited by 30 · see citing works
Clinical and pharmacologic evaluation of two dose levels of intetumumab (CNTO 95) in patients with melanoma or angiosarcoma
O'Day, S. J., Pavlick, A. C., Albertini, M. R., Hamid, O., Schalch, H., Lang, Z., Ling, J., Mata, M., Reddy, M. P., & Foster, B. J. (2011) · Investigational New Drugs · doi:10.1007/s10637-011-9639-z · Cited by 28 · see citing works
“IL-2 is associated with severe dose-related toxicities and exhibits limited efficacy [5].”
Generation of RAGE‐1 and MAGE‐9 peptide‐specific cytotoxic T‐Lymphocyte lines for transfer in patients with renal cell carcinoma
Oehlrich, N., Devitt, G., Linnebacher, M., Schwitalle, Y., Groβkinski, S., Stevanović, S., & Zöller, M. (2005) · International Journal of Cancer · doi:10.1002/ijc.21200 · Cited by 27 · see citing works
4-1BB Signaling in Conventional T Cells Drives IL-2 Production That Overcomes CD4+CD25+FoxP3+ T Regulatory Cell Suppression
Barsoumian, H. B., Yolcu, E. S., & Shirwan, H. (2016) · PLoS ONE · doi:10.1371/journal.pone.0153088 · Cited by 26 · see citing works
“IL-2 has been used as monotherapy and in combination with chemotherapy or biologics for the treatment of cancer with significant clinical benefit for melanoma and renal cell carcinoma patients [48].”
Method
Prevention of hepatocellular carcinoma in mice by IL-2 and B7-1 genes co-transfected liver cancer cell vaccines
Ge, N. (2003) · World Journal of Gastroenterology · doi:10.3748/wjg.v9.i10.2182 · Cited by 24 · see citing works
Recent Advances in Glycopeptide and Glycoprotein Synthesis: A Refined Synthetic Probe towards the Biological World
Zhuang, H., Hao, H., Qiu, Y., Gan, J., & Li, T. (2023) · Chinese Journal of Chemistry · doi:10.1002/cjoc.202300035 · Cited by 23 · see citing works
Genetically modified IL2 bone-marrow-derived myeloid cells reprogram the glioma immunosuppressive tumor microenvironment
Canella, A., Nazzaro, M., Rajendran, S. H., Schmitt, C., Haffey, A., Nigita, G., Thomas, D., Lyberger, J. M., Behbehani, G. K., Amankulor, N., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112891 · Cited by 23 · see citing works
Tumor vaccines in 2010: Need for integration
Koos, D., Josephs, S. F., Alexandrescu, D. T., Chan, R. C., Ramos, F., Bogin, V., Gammill, V., Dasanu, C. A., de Necochea-Campion, R., Riordan, N. H., et al. (2010) · Cellular Immunology · doi:10.1016/j.cellimm.2010.03.019 · Cited by 23 · see citing works
Endostatin gene therapy enhances the efficacy of IL-2 in suppressing metastatic renal cell carcinoma in mice
Rocha, F. G. D. G., Chaves, K. C. B., Chammas, R. J., Peron, J. P. S., Rizzo, L. V., Schor, N., & Bellini, M. H. (2010) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-010-0865-6 · Cited by 24 · see citing works
“demonstrated by long-term follow-up studies [11–15].”
Breast cancer gene therapy using an adenovirus encoding human IL-2 under control of mammaglobin promoter/enhancer sequences
Chaurasiya, S., Hew, P., Crosley, P., Sharon, D. M., Potts, K. G., Agopsowicz, K. C., Long, M., Shi, C., & Hitt, M. (2016) · Cancer Gene Therapy · doi:10.1038/cgt.2016.18 · Cited by 22 · see citing works
Comparative dose-responses of recombinant human IL-2 and IL-7 on STAT5 phosphorylation in CD4+FOXP3− cells versus regulatory T cells: A whole blood perspective
Dupont, G., Demaret, J., Venet, F., Malergue, F., Malcus, C., Poitevin‐Later, F., Morel, J., & Monneret, G. (2014) · Cytokine · doi:10.1016/j.cyto.2014.05.021 · Cited by 20 · see citing works
Efficacy of intraperitoneal thermochemotherapy and immunotherapy in intraperitoneal recurrence after gastrointestinal cancer resection
Fu, Q. (2002) · World Journal of Gastroenterology · doi:10.3748/wjg.v8.i6.1019 · Cited by 20 · see citing works
Targeted therapy for metastatic melanoma.
Amaravadi, R. K., & Flaherty, K. T. (2007) · PubMed · Cited by 20 · see citing works
Successful treatment by tocilizumab without steroid in a very severe case of TAFRO syndrome
Fujiki, T., Hirasawa, S., Watanabe, S., Iwamoto, S., & Ando, R. (2017) · CEN Case Reports · doi:10.1007/s13730-017-0253-6 · Cited by 19 · see citing works
Structurally diverse diterpenoid alkaloids from the lateral roots of Aconitum carmichaelii Debx. and their anti-tumor activities based on in vitro systematic evaluation and network pharmacology analysis
Yu, Y., Wu, S., Zhang, J., Li, J., Yao, C., Wu, W., Wang, Y., Ji, H., Wei, W., Gao, M., et al. (2021) · RSC Advances · doi:10.1039/d1ra04223h · Cited by 19 · see citing works
Gene Expression Profiling and Pathway Network Analysis Predicts a Novel Antitumor Function for a Botanical-Derived Drug, PG2
Kuo, Y.-L., Chen, C., Chuang, T., Hua, W.-K., Lin, W., Hsu, W., Chang, P. M., Hsu, S., Huang, T., Kao, C.-Y., et al. (2015) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2015/917345 · Cited by 19 · see citing works
“Immunotherapy regimens, such as IL-2 [33], IFN-𝛼 [34], and 𝛼-galactosylceramide (𝛼-GalCer), have been approved for routine clinical use in oncology [35].”
BackgroundInfluential
Flu-Like Syndrome and Cytokines
Descotes, J., & Vial, T. (2007) · Methods in pharmacology and toxicology · doi:10.1007/978-1-59745-350-9_10 · Cited by 19 · see citing works
Interleukin-2 in the Treatment of Renal Cell Carcinoma and Malignant Melanoma
Eklund, J. W., & Kuzel, T. M. (2005) · Cancer treatment and research · doi:10.1007/0-387-24361-5_11 · Cited by 19 · see citing works
Expression of ζ in T Cells Prior to Interleukin-2 Therapy as a Predictor of Response and Survival in Patients with Ovarian Carcinoma
Kuss, I., Rabinowich, H., Gooding, W. E., Edwards, R. P., & Whiteside, T. L. (2002) · Cancer Biotherapy and Radiopharmaceuticals · doi:10.1089/108497802320970235 · Cited by 19 · see citing works
Targeted Cytokine Delivery for Cancer Treatment: Engineering and Biological Effects
Rybchenko, V. S., Aliev, T. K., Панина, А. А., Kirpichnikov, M. P., & Dolgikh, D. A. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020336 · Cited by 18 · see citing works
“However, the limited success of IL-2 therapy might be explained by a narrow therapeutic index, vascular leakage syndrome, and toxicities, which make IL-2 more useful combined with chemotherapy [55].”
T-cell clonotypes in cancer
Straten, P. T., Schrama, D., Andersen, M. H., & Becker, J. C. (2004) · Journal of Translational Medicine · doi:10.1186/1479-5876-2-11 · Cited by 18 · see citing works
Recombinant vaccinia virus expressing IL-2 generates effective anti-tumor responses in an orthotopic murine model of head and neck carcinoma
Dasgupta, S., Tripathi, P., Bhattacharya‐Chatterjee, M., O'Malley, B., & Chatterjee, S. K. (2003) · Molecular Therapy · doi:10.1016/s1525-0016(03)00148-5 · Cited by 18 · see citing works
CD4 + CD25 + REGULATORY TC ELLS AND THEIR THERAPEUTIC POTENTIAL
Randolph, D. A., & Fathman, C. G. (2006) · Cited by 17 · see citing works
Influence of Immunotherapy With Interferon-α on Regulatory T Cells in Renal Cell Carcinoma Patients
Tatsugami, K., Eto, M., & Naito, S. (2009) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2009.0014 · Cited by 17 · see citing works
“Interleukin (IL)-2 is also considered to be central to T-cell-dependent immune responses in regulating T-cell proliferation and function (Atkins 2002).”
Immunotherapy with histamine and interleukin 2 in malignant melanoma with liver metastasis
Agarwala, S. S., Hellstrand, K., Gehlsen, K. R., & Naredi, P. L. J. (2004) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-004-0537-5 · Cited by 17 · see citing works
“IL-2 therapy, which aims at expanding and activating tumoricidal lymphocytes, induces complete regression of melanoma metastases in 3–5% of treated patients, but the toxicity of many IL-2 regimens limits its use [ 2 ].”
Background
Community-acquired methicillin-resistant Staphylococcus aureus provoked cytokine storm causing severe infection on BALB/c mice
Liao, F., Gu, W., Fu, X., Yuan, B., & Zhang, Y. (2021) · Molecular Immunology · doi:10.1016/j.molimm.2021.10.013 · Cited by 16 · see citing works
Interleukin-2 Immunotherapy of Murine Cytomegalovirus Retinitis during MAIDS Correlates with Increased Intraocular CD8+ T-Cell Infiltration
Dix, R. D., & Cousins, S. W. (2003) · Ophthalmic Research · doi:10.1159/000070051 · Cited by 16 · see citing works
Immunotherapy of Melanoma
Rietschel, P., & Chapman, P. B. (2006) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2006.02.005 · Cited by 16 · see citing works
How does the immune system attack cancer?
Morse, M. A., Lyerly, H. K., Clay, T. M., Abdel-Wahab, O. I., Chui, S. Y., Garst, J. L., Gollob, J., Grossi, P. M., Kalady, M. F., Mosca, P. J., et al. (2004) · Current Problems in Surgery · doi:10.1016/j.cpsurg.2003.08.001 · Cited by 15 · see citing works
Cytokine therapy for combating animal and human diseases – A review
Dhama, K., Chakraborty, S., Wani, M. Y., Tiwari, R., & Barathidasan, R. (2013) · Research opinions in animal & veterinary sciences · Cited by 14 · see citing works
Making the transition from hospital to home: Caring for the newly diagnosed
Jacob, E. (1999) · Home Care Provider · doi:10.1016/s1084-628x(99)90106-5 · Cited by 14 · see citing works
Initial Clinical Response Predicts Outcome and Is Associated With Dose Schedule in Metastatic Melanoma and Renal Cell Carcinoma Patients Treated With High-Dose Interleukin 2
Spanknebel, K., Cheung, K., Stoutenburg, J., Hurst-Wicker, K. S., Hesdorffer, C., DeRaffele, G., & Kaufman, A. H. L. (2005) · Annals of Surgical Oncology · doi:10.1245/aso.2005.03.063 · Cited by 14 · see citing works
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Authors: Atkins, M. B.
Affiliations: Beth Israel Deaconess Medical Center (US)
Corresponding author: Atkins, Michael B.
ORCID: Atkins, Michael B.
Venue: Seminars in Oncology
Publisher: Elsevier BV
Published: 2002-06
Volume: 29
Issue: 3
Pages: 12-17
ISSN: 0093-7754 (ISSN-L)
DOI: 10.1053/sonc.2002.33077
OpenAlex: W2114239197
Cited by: 156
References: 65
Citations by year: 2025: 1 · 2024: 3 · 2023: 6 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 7 · 2015: 6 · 2014: 6 · 2013: 6 · 2012: 6
FWCI: 1.28
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Seminars in Oncology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
Keywords: interleukin-2, immunotherapy, metastatic melanoma, acute myeloid leukemia, metastatic renal cell carcinoma, low-dose interleukin-2, dose-limiting toxicity, biochemotherapy, combination therapy, tumor response, survival
MeSH terms: Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Renal Cell, Clinical Trials as Topic, Humans, Immunologic Factors, Interleukin-2, Kidney Neoplasms, Melanoma, Leukemia, Myeloid, Acute, Immunotherapy, Active

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