April 2014 Edition
Submit You Manuscript to Win a Best Paper Award!
Dear Colleagues,
We are excited to announce that the Society for Immunotherapy of Cancer is sponsoring two new $1,000 USD awards for manuscripts published in the Journal for ImmunoTherapy of Cancer (JITC)! The JITC Best Clinical Application Paper and the JITC Best Basic Science Paper Awards will celebrate excellence in scientific research and be awarded to researchers demonstrating leadership in the field as well as innovation and high-quality execution and discussion in their manuscripts.
Award winners will be announced and highlighted at the SITC 2014 Annual Meeting & Associated Programs in National Harbor, MD from November 6-9, 2014. Along with their $1,000 prize, recipients will also be featured in Society publications, and to SITC’s constituency group of more than 5,000 experts in the field.
Time is limited so make sure to submit your manuscript to JITC before it’s too late! Only manuscripts published by August 19, 2014 will be considered. Eligible articles must be authored by a SITC member and be original research. SITC members, don’t forget to contact the SITC office for your membership code to receive waived article processing charges when you submit your research to JITC.
For more information regarding the SITC Best Paper Awards please visit http://www.sitcancer.org/journal or contact info@sitcancer.org
We look forward to reviewing your submissions.
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Below are the abstracts of articles published in this month's issue:
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Prolonged Repeated Vaccine Immuno-Chemotherapy Induces Long-Term Clinical Responses and Survival for Advanced Metastatic Melanoma |
| Coventry BJ, Lilly CA, Hersey P, Michele A and Bright RJ Journal for ImmunoTherapy of Cancer 2014, 2:9 (15 April 2014) |
Background
Repetitive long-term Vaccinia Melanoma Cell Lysate (VMCL) vaccination schedules have proved clinically effective in producing Complete Responses and strong durable survivals for up to 6.1 years in a previous study of patients with advanced Stage IV and Stage IIIc melanoma. These studies were expanded to include 54 patients for further evaluation of these findings.
Methods
54 patients comprising 48 Stage IV (6 M1a, 14 M1b, 28 M1c) and 6 advanced Stage III (5
IIIc; 1 IIIb) were studied using repeated intra-dermal VMCL vaccine therapy. If disease progressed, vaccine was continued together with standard chemotherapy (DTIC and/or Fotemustine). Overall survival was the primary end-point assessed, with clinical responses and toxicity recorded.
Results
From vaccine commencement, median overall survival was 14 months, ranging from 4 to 121 months. Kaplan-Meier survival analysis demonstrated overall 1, 2 and 3-year survival estimates of 57%, 26% and 18.5% respectively, and overall 5-year survival of 15.4%. No appreciable toxicity was observed. Complete Responses (CR) occurred in 16.7% (9) and partial responses (PR) in 14.8% (8) of patients. Stable disease was noted in a further 25 patients (46.3%). No response to therapy was apparent in 12 patients (22.2%). The overall response rate was 31.5% (CR + PR), with clinically significant responses (CR + PR + SD) in 77.8% of patients. Strong, durable clinical responses with overall survivals ≥ 23 months occurred in 29.6% of patients treated with repeated VMCL vaccine for advanced melanoma, (+/- concurrent chemotherapy).
Conclusions
Prolonged, repetitive VMCL vaccination immunotherapy appears to be a clinically effective means of generating relatively high CR rates, useful clinical responses and long-term survivals, with little toxicity, but remains notably under-explored. Successive immunomodulation might explain the results. Closer analysis of repetitive dosing is required to improve clinical response rates and survival, perhaps by optimizing the timing of immunotherapy delivery.
“Repeated, prolonged melanoma vaccinations appear to induce Immune synchronization to break tumor-induced tolerance with improved clinical responses and 5-year survivals,” noted Dr. Brendon Coventry, corresponding author and SITC Member. “Cancer vaccines are back on the agenda as effective agents, and with the new knowledge concerning dose timing are requiring renewed investigation.”
To access the full article, please click here.
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The Histone Deacetylase Inhibitor, LBH589, Promotes the Systemic Cytokine and Effector Responses of Adoptively Transferred CD8+ T cells |
| Lisiero DN, Soto H, Everson RG, Liau LM and Prins RM Journal for ImmunoTherapy of Cancer 2014, 2:8 (15 April 2014) |
Background
Histone deacetylase (HDAC) inhibitors are a class of agents that have potent antitumor activity with a reported ability to upregulate MHC and costimulatory molecule expression. We hypothesized that epigenetic pharmacological immunomodulation could sensitize tumors to immune mediated cell death with an adoptive T cell therapy.
Methods
The pan-HDAC inhibitor, LBH589, was combined with gp100 specific T cell immunotherapy in an in vivo B16 melanoma model and in an in vivo non-tumor bearing model. Tumor regression, tumor specific T cell function and phenotype, and serum cytokine levels were evaluated.
Results
Addition of LBH589 to an adoptive cell transfer therapy significantly decreased tumor burden while sustaining systemic pro-inflammatory levels. Furthermore, LBH589 was able to enhance gp100 specific T cell survival and significantly decrease T regulatory cell populations systemically and intratumorally. Even in the absence of tumor, LBH589 was able to enhance the proliferation, retention and polyfunctional status of tumor specific T cells, suggesting its effects were T cell specific. In addition, LBH589 induced significantly higher levels of the IL-2 receptor (CD25) and the co-stimulatory molecule OX-40 in T cells.
Conclusion
These results demonstrate that immunomodulation of adoptively transferred T cells by LBH589 provides a novel mechanism to increase in vivo antitumor efficacy of effector CD8 T cells.
"The findings in this article demonstrate the ability of the pan-histone deacetylase inhibitor, LBH589, to act as a potent adjuvant for adoptive T cell transfer therapy in the treatment of solid tumors,” noted Dominique N. Lisiero, corresponding author. “LBH589 enhanced retention of tumor specific CD8+ T cells and promoted a systemic pro-inflammatory environment comprised of sustained TNF and IFN-gamma in the serum. These results suggest that regulation of CD8+ T cell function by histone deacetylase inhibitors can provide a significant therapeutic benefit.”
To access the full article, please click here.
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Targeting Tumor-Necrosis Factor Receptor Pathways for Tumor Immunotherapy |
| Schaer DA, Hirschhorn-Cymerman D and Wolchok JD Journal for ImmunoTherapy of Cancer 2014, 2:7 (15 April 2014) |
Full Abstract
With the success of ipilimumab and promise of programmed death-1 pathway-targeted agents, the field of tumor immunotherapy is expanding rapidly. Newer targets for clinical development include select members of the tumor necrosis factor receptor (TNFR) family.
Agonist antibodies to these co-stimulatory molecules target both T and B cells, modulating T-cell activation and enhancing immune responses. In vitro and in vivo preclinical data have provided the basis for continued development of 4-1BB, OX40, glucocorticoid-induced TNFR-related gene, herpes virus entry mediator, and CD27 as potential therapies for patients with cancer. In this review, we summarize the immune response to tumors, consider preclinical and early clinical data on select TNFR family members, discuss potential translational challenges and suggest possible combination therapies with the aim of inducing durable antitumor responses.
"With the success and experience gained blocking co-inhibitory receptors for cancer immunotherapy, activating co-stimulatory receptors may represent the next step at extending clinical benefit to more patients,” stated Dr. David Schaer, corresponding author and SITC Member. “In this review, we give a brief overview of the potential for targeting co-stimulatory members of the TNF receptor superfamily"
To access the full article, please click here.
Highly Accessed Article Update
Below are two highly accessed research articles from the month of March:
Stem Cells and Cancer Immunotherapy: Arrowhead’s 2nd Annual Cancer Immunotherapy Conference
Bot A, Chiriva-Internati M, Cornforth A, Czerniecki BJ, Ferrone S, Geles K, Greenberg PD, Hurt E et al. Journal for ImmunoTherapy of Cancer 2014, 2:6 (20 March 2014)
Very Small Size Proteoliposomes Abrogate Cross-Presentation of Tumor Antigens by Myeloid-Derived Suppressor Cells and Induce Their Differentiation to Dendritic Cells
Fernández A, Oliver L, Alvarez R, Hernández A, Raymond J, Fernández LE and Mesa C
Journal for ImmunoTherapy of Cancer 2014, 2:5 (11 March 2014)
Waived Article Processing Charges for SITC Members
SITC members – Don’t forget to take advantage of waived article processing charges when you submit your research to JITC (a $2,400 USD savings). For your membership code, please contact the SITC office at +1(414) 271-2456.
Need to renew your membership dues for 2014 or become a SITC Member to take advantage of this benefit? Simply click here.
SITC Members and non-members alike are invited to submit their manuscript in the following categories:
- Basic Tumor Immunology
Section Editor: Cornelis J.M. Melief, MD, PhD - ISA Therapeutics BV
Topics Include: tumor antigens, innate and adaptive anti-tumor immune mechanisms, immune regulation, immune response, cancer and inflammation, preclinical models, chemotherapy and radiotherapy interactions with the anti-tumor immune response, oncolytic viruses
- Case Reports
Section Editor: F. Stephen Hodi, Jr., MD - Dana-Farber Cancer Institute
Topics Include: unusual or unexpected clinical cases that expand the field of general medical knowledge
- Clinical/Translational Cancer Immunotherapy
Section Editor: Walter J. Urba, MD, PhD - Earle A. Chiles Research Institute
Topics Include: first in man clinical trials, phase II/III clinical studies, immune monitoring investigations, tumor microenvironment, host genetics and clinical outcome, updates on clinical trials
- Immunotherapy Biomarkers:
Section Editor: Lisa H. Butterfield, PhD - University of Pittsburgh Cancer Institute
Topics Include: predictive/prognostic biomarker studies, gene expression studies in cancer immunotherapy, serological immune biomarkers, multiparameter flow cytometry-defined immune biomarkers, high content immunohistological studies
- Reviews/Editorials:
Section Editors: Bernard A. Fox, PhD - Earle A. Chiles Research Institute and Thomas F. Gajewski, MD, PhD - University of Chicago
Topics include: discussion on hot topics and innovative concepts
JITC Editor-in-Chief
Pedro J. Romero, MD - Ludwig Center for Cancer Research
To submit your research visit: www.sitcancer.org/journal
