Research Topics
Genomes and Genes | Paul M SondelSummaryAffiliation: University of Wisconsin Country: USA Publications
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Publications
A phase I clinical trial of the hu14.18-IL2 (EMD 273063) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: a study of the Children's Oncology GroupKaci L Osenga
The University of Wisconsin-Madison, Madison, Wisconsin, USA
Clin Cancer Res 12:1750-9. 2006..A phase II clinical trial of hu14.18-IL2, administered at a dose of 12 mg/m2/d x 3 days repeated every 28 days, will be done in pediatric patients with recurrent/refractory neuroblastoma...- Pleasant memories: remembering immune protection while forgetting about graft-versus-host diseasePaul M Sondel
Department of Pediatrics, University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53792, USA
J Clin Invest 112:25-7. 2003 
Preclinical and clinical development of immunocytokinesPaul M Sondel
Department of Pediatrics, Human Oncology, Genetics and Medicine and the University of Wisconsin Comprehensive Cancer Center, The University of Wisconsin Madison, 600 Highland Avenue, Madison, WI 53792, USA
Curr Opin Investig Drugs 4:696-700. 2003..Clinical testing of ICs has recently begun using an anti-GD2 monoclonal antibody linked to interleukin-2 (IL-2) (hu14.18-IL-2), and using an antibody directed against the human epithelial cell adhesion molecule linked to IL-2 (KS-IL-2)...- In vivo CD40 ligation can induce T-cell-independent antitumor effects that involve macrophagesHillary D Lum
Department of Human Oncology, University of Wisconsin, Madison, WI 53792, USA
J Leukoc Biol 79:1181-92. 2006..Taken together, our results show that anti-CD40 mAb immunotherapy of mice can inhibit tumor growth in the absence of T cells, NK cells, and PMN through the involvement of activated Mphi... - Macrophages are essential for antitumour effects against weakly immunogenic murine tumours induced by class B CpG-oligodeoxynucleotidesIlia N Buhtoiarov
Department of Human Oncology, The University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 4672, USA
Immunology 120:412-23. 2007..Taken together, our results indicate that the growth control of weakly immunogenic tumours during CpG-immunotherapy is mediated predominantly by Mphi, rather than T cells or NK cells... - Tumor-associated myeloid cells can be activated in vitro and in vivo to mediate antitumor effectsAlexander L Rakhmilevich
Department of Human Oncology, University of Wisconsin, 4136 WIMR, 1111 Highland Avenue, Madison, WI 53705, USA
Cancer Immunol Immunother 61:1683-97. 2012..Inhibition of NO did not abrogate the antitumor effects of stimulated myeloid cells. Taken together, the results indicate that in tumor-bearing hosts, tumor-associated myeloid cells can be activated to mediate antitumor effects... - Anti-tumor and immunomodulatory activity of resveratrol in vitro and its potential for combining with cancer immunotherapyBrenda L Soto
Department of Human Oncology, University of Wisconsin, Madison, WI 53706, USA
Int Immunopharmacol 11:1877-86. 2011..Results showed that this RV regimen inhibited the growth of NXS2 tumors in vivo but did not appear to interfere with blood cell count, splenocyte or macrophage function. Thus, RV may be a candidate for combining with immunotherapy... - Tumoristatic effects of anti-CD40 mAb-activated macrophages involve nitric oxide and tumour necrosis factor-alphaHillary D Lum
Department of Human Oncology, University of Wisconsin, Madison, WI 53792, USA
Immunology 118:261-70. 2006..Taken together, these results suggest that NO and TNF-alpha are involved in, but not solely responsible for, the antitumour effects of macrophages after activation by CD40 ligation... 
CD40 ligation in vivo can induce T cell independent antitumor effects even against immunogenic tumorsAlexander L Rakhmilevich
The Department of Human Oncology, University of Wisconsin, K4 413 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792, USA
Cancer Immunol Immunother 57:1151-60. 2008..Taken together, our results indicate that antitumor effects induced by alphaCD40, even against immunogenic tumors, can be observed in the absence of T cells and may involve macrophages...- Intratumoral hu14.18-IL-2 (IC) induces local and systemic antitumor effects that involve both activated T and NK cells as well as enhanced IC retentionRichard K Yang
Department of Human Oncology, University of Wisconsin, Madison, WI 53705, USA
J Immunol 189:2656-64. 2012..v.-IC. Overall, IT-IC resulted in increased numbers of activated T and NK cells within tumors, better IC retention in the tumor, enhanced inhibition of tumor growth, and improved survival compared with i.v.-IC... - Enhanced activity of hu14.18-IL2 immunocytokine against murine NXS2 neuroblastoma when combined with interleukin 2 therapyZane C Neal
Department of Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin 53792, USA
Clin Cancer Res 10:4839-47. 2004..Animals showing prolonged tumor eradication of established tumors after the combined hu14.18-IL2 plus IL-2 regimen exhibited a protective T-cell-dependent antitumor memory response against NXS2 rechallenge... - Intratumoral immunocytokine treatment results in enhanced antitumor effectsErik E Johnson
Department of Surgery, University of Wisconsin, Madison, WI, 53792, USA
Cancer Immunol Immunother 57:1891-902. 2008..Further testing is required to determine how to potentially incorporate IT administration of IC into an antitumor regimen that optimizes local and systemic anticancer therapy... - Flt3-L gene therapy enhances immunocytokine-mediated antitumor effects and induces long-term memoryZane C Neal
Mirus Bio Corporation, Madison, WI 53719, USA
Cancer Immunol Immunother 56:1765-74. 2007..Mice that received combined FL gene therapy plus IC exhibited complete and durable resolution of established NXS2 tumors, and demonstrated protection from subsequent rechallenge with NXS2 tumor... - Tumoricidal effects of activated macrophages in a mouse model of chronic lymphocytic leukemiaQing Li Wu
Department of Pathology and Laboratory Medicine, Pediatrics University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA
J Immunol 182:6771-8. 2009..Our results suggest a novel immunotherapeutic strategy for CLL that may be effective even in the face of tumor or chemotherapy-induced T cell immunodeficiency... - Immunogenicity of the hu14.18-IL2 immunocytokine molecule in adults with melanoma and children with neuroblastomaJacquelyn A Hank
The University of Wisconsin Paul P Carbone Comprehensive Cancer Center, Madison, Wisconsin 53792, USA
Clin Cancer Res 15:5923-30. 2009..18) and interleukin (IL)-2. Sixty-one melanoma and neuroblastoma patients received IC in phase I/Ib studies. Patient sera were examined in ELISA to determine if an anti-IC antibody response occurred during treatment... - Radiofrequency ablation combined with KS-IL2 immunocytokine (EMD 273066) results in an enhanced antitumor effect against murine colon adenocarcinomaErik E Johnson
Departments of Surgery, Human Oncology, and Pediatrics and Paul P Carbone Comprehensive Cancer Center, University of Wisconsin, Madison, WI 53792, USA
Clin Cancer Res 15:4875-84. 2009..Radiofrequency ablation (RFA) is a common treatment modality for surgically unresectable tumors. However, there is a high rate of both local and systemic recurrence... - Ab-IL2 fusion proteins mediate NK cell immune synapse formation by polarizing CD25 to the target cell-effector cell interfaceJennifer A A Gubbels
Department of Obstetrics and Gynecology, University of Wisconsin Madison, Madison, WI 53711, USA
Cancer Immunol Immunother 60:1789-800. 2011..These findings demonstrate that the IL-2 component of the IC allows IL2Rs to function not only as receptors for this cytokine but also as facilitators of peritoneal NK cell binding to IC-coated tumor cells... - Naive mouse macrophages become activated following recognition of L5178Y lymphoma cells via concurrent ligation of CD40, NKG2D, and CD18 moleculesIlia N Buhtoiarov
Department of Human Oncology, University of Wisconsin, Madison, WI 53792, USA
J Immunol 182:1940-53. 2009..These results suggest that contact with certain tumor cells via CD40, NKG2D, and CD18 molecules on the Mphi may facilitate Mphi-mediated antitumor immune surveillance... - Anti-tumour synergy of cytotoxic chemotherapy and anti-CD40 plus CpG-ODN immunotherapy through repolarization of tumour-associated macrophagesIlia N Buhtoiarov
Department of Human Oncology, University of Wisconsin, Madison, WI 53705 2275, USA
Immunology 132:226-39. 2011..Together, the results show that CT and anti-CD40 + CpG-ODN IT synergize in the induction of anti-tumour effects which are associated with the phenotypic repolarization of tumour-associated Mφ... - Differential internalization of hu14.18-IL2 immunocytokine by NK and tumor cell: impact on conjugation, cytotoxicity, and targetingIlia N Buhtoiarov
UW Carbone Cancer Center, 4159 MACC Fund UW Childhood Cancer Research Wing, WIMR, 1111 Highland Ave, Madison, WI 53705 2275, USA
J Leukoc Biol 89:625-38. 2011..These studies demonstrate that once IC binds to the tumor, it is present on the tumor surface for a prolonged time, inducing the recruitment of NK cells to the tumor site, followed by tumor cell killing... - Phase I trial of combined treatment with ch14.18 and R24 monoclonal antibodies and interleukin-2 for patients with melanoma or sarcomaBrian S Choi
Department of Medicine, University of Wisconsin, Madison, 53792, USA
Cancer Immunol Immunother 55:761-74. 2006..As such, the combination of these two antibodies together with IL-2 therapy appeared to influence the MTD and toxicity of each of the administered antibodies... - Synergistic activation of macrophages via CD40 and TLR9 results in T cell independent antitumor effectsIlia N Buhtoiarov
Department of Human Oncology and Comprehensive Cancer Center, University of Wisconsin, Madison, WI 53792, USA
J Immunol 176:309-18. 2006.... - Enhanced T-cell-independent antitumor effect of cyclophosphamide combined with anti-CD40 mAb and CpG in miceErik E Johnson
Paul P Carbone Comprehensive Cancer Center, Department of Surgery, University of Wisconsin, Madison, WI, USA
J Immunother 34:76-84. 2011..These results suggest that therapeutic strategies to activate macrophages may have potential for clinical application in cancer patients receiving chemotherapy... - The anti-tumor effect of resveratrol alone or in combination with immunotherapy in a neuroblastoma modelBrenda L Soto
Department of Human Oncology, University of Wisconsin, Madison, WI 53792, USA
Cancer Immunol Immunother 60:731-8. 2011..These results demonstrate that the combination therapy of peritumoral resveratrol plus intravenous immunocytokine provides better anti-tumor effects in this model than either therapy alone... - Phase II trial of hu14.18-IL2 for patients with metastatic melanomaMark R Albertini
University of Wisconsin Carbone Cancer Center, Madison, WI, USA
Cancer Immunol Immunother 61:2261-71. 2012..We conclude that subsequent testing of hu14.18-IL2 should involve melanoma patients with minimal residual disease based on compelling preclinical data and the confirmed immune activation with some antitumor activity in this study... - The development of antibody-IL-2 based immunotherapy with hu14.18-IL2 (EMD-273063) in melanoma and neuroblastomaBrett H Yamane
The University of Wisconsin Madison, Departments of Surgery, WI 53792, USA
Expert Opin Investig Drugs 18:991-1000. 2009..Preclinical and initial clinical data suggest greater efficacy in the setting of minimal residual disease; therefore, future clinical testing is planned to test the benefit of EMD-273063 in this setting... - CD40 ligation activates murine macrophages via an IFN-gamma-dependent mechanism resulting in tumor cell destruction in vitroIlia N Buhtoiarov
Department of Human Oncology and UW Comprehensive Cancer Center, University of Wisconsin, Madison, WI 53792, USA
J Immunol 174:6013-22. 2005..IFN-gamma production by macrophages was dependent on IL-12. Taken together, the results show that murine macrophages are activated directly by anti-CD40 mAb to secrete IFN-gamma and mediate tumor cell destruction... - Native and genetically engineered anti-disialoganglioside monoclonal antibody treatment of melanomaMark R Albertini
University of Wisconsin Comprehensive Cancer Center, Madison, WI 53792, USA
Cancer Chemother Biol Response Modif 22:789-97. 2005 - Genotypes of NK cell KIR receptors, their ligands, and Fcγ receptors in the response of neuroblastoma patients to Hu14.18-IL2 immunotherapyDavid C Delgado
Department of Pediatrics, University of Wisconsin, Madison, Wisconsin, USA
Cancer Res 70:9554-61. 2010..These analyses indicate that response or improvement of relapsed/refractory NBL patients after IC treatment is associated with autologous KIR/KIR-ligand mismatch, consistent with a role for natural killer cells in this clinical response... - T-cell-independent antitumor effects of CD40 ligationAlexander L Rakhmilevich
Department of Human Oncology and Paul P Carbone Comprehensive Cancer Center, University of Wisconsin Madison, Madison, WI 53705, USA
Int Rev Immunol 31:267-78. 2012..In this review the authors focus on the ability of CD40 ligation to activate antitumor effector mechanisms of the cells of innate immunity such as macrophages and NK cells... - Immunotherapy for pediatric cancerStephan A Grupp
Division of Oncology, Department of Pediatrics, Department of Pathology and Laboratory Medicine, Children s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Biol Blood Marrow Transplant 14:33-43. 2008..This review explores how 3 components of the immune system--T cells, natural killer (NK) cells, and antibodies--can be used for therapy of pediatric malignancies... - Antibody-based immunotherapy in high-risk neuroblastomaErik Johnson
Department of Surgery, The University of Wisconsin Madison, WI 53792, USA
Expert Rev Mol Med 9:1-21. 2007..Future therapies under investigation in the area of immunotherapy for neuroblastoma are considered... - Intratumoral injection of interleukin-12 plasmid DNA, either naked or in complex with cationic lipid, results in similar tumor regression in a murine modelFushun Shi
Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin 53792, USA
Mol Cancer Ther 1:949-57. 2002..These results indicate that direct intratumoral gene transfer with naked nonviral IL-12 DNA provides an effective and simple method for the treatment of murine tumors, suggesting an approach for clinical application... - A phase I study of immunization using particle-mediated epidermal delivery of genes for gp100 and GM-CSF into uninvolved skin of melanoma patientsRyan D Cassaday
Paul P Carbone Comprehensive Cancer Center, University of Wisconsin, 600 Highland Avenue, Madison, WI 53792, USA
Clin Cancer Res 13:540-9. 2007..The aims of this phase I study were to assess the safety and immunologic effects of PMED of these genes in melanoma patients... - Enhancement of the anti-melanoma response of Hu14.18K322A by αCD40 + CpGKory L Alderson
Department of Human Oncology, University of Wisconsin Madison, Madison, WI, USA
Cancer Immunol Immunother 62:665-75. 2013.... - Suppression of T-cell expansion by melanoma is exerted on resting cellsAndrew J Russ
Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
Ann Surg Oncol 18:3848-57. 2011..Immunotherapeutic cancer protocols often rely on the ability to promote proliferative expansion of tumor-specific T-cell, but the influence of cancer on in vivo T-cell expansion remains largely undefined... - Clinical cancer therapy by NK cells via antibody-dependent cell-mediated cytotoxicityKory L Alderson
Department of Human Oncology, University of Wisconsin, Madison, WI 53705, USA
J Biomed Biotechnol 2011:379123. 2011..Therefore more research is needed that focuses on evaluating which NK cell and tumor criteria are best predictive of a clinical response and which combination immunotherapy regimens to pursue for distinct clinical settings... - NXS2 murine neuroblastomas express increased levels of MHC class I antigens upon recurrence following NK-dependent immunotherapyZane C Neal
University of Wisconsin Comprehensive Cancer Center, University of Wisconsin-Madison, 600 Highland Ave, K4/448, Madison, WI 53792, USA
Cancer Immunol Immunother 53:41-52. 2004.... - Treatment of experimental breast cancer using interleukin-12 gene therapy combined with anti-vascular endothelial growth factor receptor-2 antibodyAlexander L Rakhmilevich
K4 413 Clinical Science Center, Department of Human Oncology, University of Wisconsin Madison, 600 Highland Avenue, Madison, WI 53792, USA
Mol Cancer Ther 3:969-76. 2004..Our results show a therapeutic benefit of combining IL-12 gene therapy and anti-VEGFR-2 mAb for cancer treatment... - Determination of peak serum levels and immune response to the humanized anti-ganglioside antibody-interleukin-2 immunocytokineJacquelyn A Hank
Comprehensive Cancer Center, Department of Human Oncology, University of Wisconsin, Madison, WI, USA
Methods Mol Med 85:123-31. 2003 - Safety of interleukin-12 gene therapy against cancer: a murine biodistribution and toxicity studyMichael Imboden
Department of Human Oncology, University of Wisconsin-Madison, Madison, WI 53792, USA
Hum Gene Ther 14:1037-48. 2003.... - Phase II study of oral capsular 4-hydroxyphenylretinamide (4-HPR/fenretinide) in pediatric patients with refractory or recurrent neuroblastoma: a report from the Children's Oncology GroupJudith G Villablanca
Children s Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California 90027, USA
Clin Cancer Res 17:6858-66. 2011..To determine the response rate to oral capsular fenretinide in children with recurrent or biopsy proven refractory high-risk neuroblastoma... - Up-regulation of Fas (CD95) expression in tumour cells in vivoNaama Peshes-Yaloz
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
Immunology 120:502-11. 2007..Our model is that host lymphoid cells in response to a tumour increase NO synthesis, which in turn causes enhanced Fas expression in the tumour...