Metronomic treatment in immunocompetent preclinical GL261 glioblastoma: effects of cyclophosphamide and temozolomide

Glioblastoma (GBM) causes poor survival in patients even when applying aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment, but resistance always ensues. In previous years, efforts have focused on new therapeutic regimens with conventional drugs to activate immune responses that may enhance tumor regression and prevent regrowth, for example the “metronomic” approaches. In metronomic scheduling studies, cyclophosphamide (CPA) in GL261 GBM growing subcutaneously in C57BL/6 mice was shown not only to activate antitumor CD8+ T‐cell response, but also to induce long‐term specific T‐cell tumor memory.

[1]  Nicolas André,et al.  Metronomic chemotherapy: new rationale for new directions , 2010, Nature Reviews Clinical Oncology.

[2]  Jan C Buckner,et al.  Factors influencing survival in high-grade gliomas. , 2003, Seminars in oncology.

[3]  F. Mami-Chouaib,et al.  T-cell modulatory properties of CD5 and its role in antitumor immune responses , 2013, Oncoimmunology.

[4]  C. Rübe,et al.  Toxicity after radiochemotherapy for glioblastoma using temozolomide - a retrospective evaluation , 2011, Radiation oncology.

[5]  P. Anderson,et al.  Outpatient chemotherapy plus radiotherapy in sarcomas: improving cancer control with radiosensitizing agents. , 2008, Cancer control : journal of the Moffitt Cancer Center.

[6]  P. Knopf,et al.  Drainage of Brain Extracellular Fluid into Blood and Deep Cervical Lymph and its Immunological Significance , 1992, Brain pathology.

[7]  Patrick Y Wen,et al.  Application of Novel Response/Progression Measures for Surgically Delivered Therapies for Gliomas: Response Assessment in Neuro-Oncology (RANO) Working Group , 2012, Neurosurgery.

[8]  C. Takimoto.  Maximum tolerated dose: clinical endpoint for a bygone era? , 2009, Targeted Oncology.

[9]  S. Crawford.  Is it time for a new paradigm for systemic cancer treatment? Lessons from a century of cancer chemotherapy , 2013, Front. Pharmacol..

[10]  P. Siesjö,et al.  Intratumoral temozolomide synergizes with immunotherapy in a T cell-dependent fashion , 2013, Cancer Immunology, Immunotherapy.

[11]  Qiulian Wu,et al.  Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting , 2010, Protein & Cell.

[12]  R. Mirimanoff,et al.  Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. , 2009, The Lancet. Oncology.

[13]  S. Ortega-Martorell,et al.  Improving the classification of brain tumors in mice with perturbation enhanced (PE)-MRSI , 2010, Integrative biology : quantitative biosciences from nano to macro.

[14]  D. Waxman,et al.  Metronomic cyclophosphamide eradicates large implanted GL261 gliomas by activating antitumor Cd8+ T-cell responses and immune memory , 2015, Oncoimmunology.

[15]  D. Waxman,et al.  Metronomic cyclophosphamide schedule-dependence of innate immune cell recruitment and tumor regression in an implanted glioma model. , 2014, Cancer Letters.

[16]  D. Waxman,et al.  Metronomic cyclophosphamide activation of anti-tumor immunity: tumor model, mouse host, and drug schedule dependence of gene responses and their upstream regulators , 2016, BMC Cancer.

[17]  L. Bracci,et al.  Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer , 2013, Cell Death and Differentiation.

[18]  Paulo J. G. Lisboa,et al.  A Novel Semi-Supervised Methodology for Extracting Tumor Type-Specific MRS Sources in Human Brain Data , 2013, PloS one.

[19]  I. Fidler,et al.  Orthotopic Models are Necessary to Predict Therapy of Transplantable Tumors in Mice , 1998, Cancer and Metastasis Reviews.

[20]  G. Ingravallo,et al.  Erdheim-Chester disease: a systematic review. , 2015, Critical reviews in oncology/hematology.

[21]  M. Julià-Sapé,et al.  Molecular imaging coupled to pattern recognition distinguishes response to temozolomide in preclinical glioblastoma , 2014, NMR in biomedicine.

[22]  Kristen L. Jones,et al.  Glioblastoma Eradication Following Immune Checkpoint Blockade in an Orthotopic, Immunocompetent Model , 2015, Cancer Immunology Research.

[23]  Sabine Van Huffel,et al.  Fast nosological imaging using canonical correlation analysis of brain data obtained by two‐dimensional turbo spectroscopic imaging , 2008, NMR in biomedicine.

[24]  P. Lowenstein,et al.  Overview of current immunotherapeutic strategies for glioma. , 2015, Immunotherapy.

[25]  Jean-Philippe Galons,et al.  Early response of prostate carcinoma xenografts to docetaxel chemotherapy monitored with diffusion MRI. , 2002, Neoplasia.

[26]  Mark S. Kindy,et al.  A therapeutic cancer vaccine against GL261 murine glioma , 2016, Journal of Translational Medicine.

[27]  Sandra Ortega-Martorell,et al.  Pattern Recognition Analysis of MR Spectra , 2016 .

[28]  V. Lorusso,et al.  Metronomic chemotherapy from rationale to clinical studies: a dream or reality? , 2015, Critical reviews in oncology/hematology.

[29]  W. Zong,et al.  Necrotic death as a cell fate. , 2006, Genes & development.

[30]  L. Schwartz,et al.  New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). , 2009, European journal of cancer.

[31]  H. Hamada,et al.  Detailed characterization of the mouse glioma 261 tumor model for experimental glioblastoma therapy , 2006, Cancer science.

[32]  Yong Loo,et al.  Advances and challenges in the molecular biology and treatment of glioblastoma-is there any hope for the future? , 2015, Annals of translational medicine.

[33]  H. Geiger,et al.  Mutagenic potential of temozolomide in bone marrow cells in vivo. , 2005, Blood.

[34]  C. Arús,et al.  Development of a transplantable glioma tumour model from genetically engineered mice: MRI/MRS/MRSI characterisation , 2016, Journal of Neuro-Oncology.

[35]  M. Chamberlain,et al.  Salvage chemotherapy with cyclophosphamide for recurrent, temozolomide‐refractory glioblastoma multiforme , 2004, Cancer.

[36]  C. Arús,et al.  1H‐MRSI pattern perturbation in a mouse glioma: the effects of acute hyperglycemia and moderate hypothermia , 2010, NMR in biomedicine.

[37]  P. Marchetti,et al.  Metronomic chemotherapy for cancer treatment: a decade of clinical studies , 2013, Cancer Chemotherapy and Pharmacology.

[38]  K. Partanen,et al.  Oncolytic adenovirus with temozolomide induces autophagy and antitumor immune responses in cancer patients. , 2013, Molecular therapy : the journal of the American Society of Gene Therapy.

[39]  Changying Ling,et al.  Initiation of Immune Responses in Brain Is Promoted by Local Dendritic Cells1 , 2004, The Journal of Immunology.

[40]  D. Hicklin,et al.  A Comparative Analysis of Low-Dose Metronomic Cyclophosphamide Reveals Absent or Low-Grade Toxicity on Tissues Highly Sensitive to the Toxic Effects of Maximum Tolerated Dose Regimens , 2004, Cancer Research.

[41]  C Arús,et al.  Perturbation of mouse glioma MRS pattern by induced acute hyperglycemia , 2008, NMR in biomedicine.

[42]  E. Hattingen,et al.  Bevacizumab impairs oxidative energy metabolism and shows antitumoral effects in recurrent glioblastomas: a 31P/1H MRSI and quantitative magnetic resonance imaging study. , 2011, Neuro-oncology.

[43]  Abhishek D. Garg,et al.  Dendritic cell vaccines based on immunogenic cell death elicit danger signals and T cell–driven rejection of high-grade glioma , 2016, Science Translational Medicine.

[44]  N. Pouratian,et al.  Non-Hodgkin's lymphoma in patients with glioma treated with temozolomide. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  Peter Bohlen,et al.  Antitumor effects in mice of low-dose (metronomic) cyclophosphamide administered continuously through the drinking water. , 2002, Cancer research.

[46]  Jennie W. Taylor,et al.  Plasmablastic lymphoma after standard-dose temozolomide for newly diagnosed glioblastoma , 2013, Neurology.

[47]  L. Galluzzi,et al.  Trial watch , 2012, Oncoimmunology.

[48]  S. Russell,et al.  Cellular immune response against firefly luciferase after sleeping beauty-mediated gene transfer in vivo. , 2014, Human gene therapy.

[49]  G. Bocci,et al.  Cyclophosphamide-based metronomic chemotherapy: after 10 years of experience, where do we stand and where are we going? , 2012, Critical reviews in oncology/hematology.

[50]  Paulo J. G. Lisboa,et al.  Convex Non-Negative Matrix Factorization for Brain Tumor Delimitation from MRSI Data , 2012, PloS one.

[51]  M. Christmann,et al.  BER, MGMT, and MMR in defense against alkylation-induced genotoxicity and apoptosis. , 2001, Progress in nucleic acid research and molecular biology.

[52]  C Arús,et al.  MRSI‐based molecular imaging of therapy response to temozolomide in preclinical glioblastoma using source analysis , 2016, NMR in biomedicine.

[53]  N. André,et al.  Concentration- and schedule-dependent effects of chemotherapy on the angiogenic potential and drug sensitivity of vascular endothelial cells , 2012, Angiogenesis.

[54]  Y. Liu,et al.  Histopathological findings in the peritumoral edema area of human glioma. , 2015, Histology and Histopathology.

[55]  D. Rall,et al.  Studies on the chemotherapy of experimental brain tumors: development of an experimental model. , 1970, Cancer research.

[56]  Gabriele Bergers,et al.  Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. , 2000, The Journal of clinical investigation.

[57]  Kelvin K. W. Chan,et al.  Low-dose metronomic chemotherapy: a systematic literature analysis. , 2013, European journal of cancer.

[58]  Dieta Brandsma,et al.  Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. , 2008, The Lancet. Oncology.