January 2014 Edition
Announcing JITC Indexed in PubMed
Less than a year after its first issue, SITC received the good news that the Journal for ImmunoTherapy of Cancer was accepted to PubMed and PubMed Central. This is an exciting step in the evolution of JITC as we can now offer greater visibility and accessibility to all articles submitted to our Journal – the only journal specifically focused on all aspects of tumor immunology and cancer immunotherapy.
Inclusion in PubMed and PubMed Central will make it easier for all scientists, clinicians, patients, educators and students to find, read and cite YOUR articles. All previously published and future articles will be indexed in PubMed and PubMed Central in the near future. Look for future announcements when all articles have been added.
NOW is the perfect time to submit your research to JITC and to take advantage of:
- Efficient online submission process
- Rapid, high quality peer-review service by an internationally renowned Editorial Board
- Distribution of your article to over 15,000 individuals in the cancer treatment space upon publication
- Inclusion in freely accessible full text repositories
- Compliance with the open access policies of many funders including those of the Howard Hughes Medical Institute, NIH, and Wellcome Trust
As a thank you to the dedicated SITC members who work tirelessly to advance the science and ultimately to improve the lives of patients with cancer, we are happy to announce that once again SITC will waive article processing charges for SITC members through 2014 (a $2,400 USD savings). Don’t miss the opportunity to take advantage of this exclusive member benefit!
For more information or to claim your member submission code, please contact the SITC office at +1 414 271 2456 or at info@sitcancer.org
January Articles – NOW Available
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Immunoglobulin-like Transcript 2 (ILT2) is a Biomarker of Therapeutic Response to Oncolytic Immunotherapy with Vaccinia Viruses |
| Andrew Zloza, Dae Won Kim, Seunghee Kim-Schulze, Michael C. Jagoda, Vladia Monsurro, Francesco M. Marincola, and Howard L. Kaufman Journal for ImmunoTherapy of Cancer 2014, 2:1 (27 January 2014) |
Background: Oncolytic viruses represent a novel form of cancer immunotherapy. Vaccinia viruses encoding human T cell co-stimulatory molecules have demonstrated clinical activity in phase I clinical trials in patients with advanced melanoma. However, predictive biomarkers of therapeutic response have not yet been identified.
Methods: A customized microarray was performed to identify changes in peripheral blood mononuclear cell (PBMC) gene expression upon exposure to recombinant oncolytic vaccinia viruses. Up-regulated and down-regulated genes were identified and selected for further analysis using PBMC samples from normal donors and oncolytic virus-treated patients before and after viral injection. Quantitative PCR and flow cytometry of defined T cell subsets was performed to evaluate expression patterns and clinical correlations.
Results: The microarray identified 301 genes that were up-regulated and 960 genes that were down-regulated in T cells after exposure to oncolytic vaccinia virus. The B7.1 gene was highly up-regulated and the immunoglobulin-like transcript 2 (ILT2) gene was highly down-regulated by vaccinia-B7.1, which was consistent with the known inverse regulation of these two genes. We observed an inverse association between ILT2 expression in the tumor microenvironment and clinical response and further identified ILT2 as a marker of regulatory CD4+ and suppressor CD8+ T cell responses and whose down-regulation was predictive of therapeutic responses in patients treated with oncolytic virus immunotherapy.
"The identification of predictive biomarkers is a high priority for the field of tumor immunotherapy,” stated Dr. Howard L. Kaufman, corresponding author on the paper. “We found immunoglobulin-like 2 (ILT2) expression on T cells was inversely associated with clinical response in a small cohort of melanoma patients treated with an oncolytic vaccinia virus.” Additionally Dr. Kaufman noted that “while this finding requires further prospective validation, the data suggests that the ILT2 T cell checkpoint may be a novel predictive biomarker in immunotherapy and could also be a new therapeutic target for future immunotherapy drug development."
To read the full article in JITC, click here.
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Recombinant Interleukin-21 plus Sorafenib for Metastatic Renal Cell Carcinoma: A Phase 1/2 Study |
| Shailender Bhatia, Brendan Curti, Marc S Ernstoff, Michael Gordon, Elisabeth I Heath, Wilson H Miller (Jr), Igor Puzanov, David I Quinn, Thomas W. Flaig, Peter VanVeldhuizen, Kelly Byrnes-Blake, Jeremy A Freeman, Rachel Bittner, Naomi Hunder, Sonia Souza, John A Thompson Journal for ImmunoTherapy of Cancer 2014, 2:2 (27 January 2014) |
Purpose: Despite the positive impact of targeted therapies on metastatic renal cell carcinoma (mRCC), durable responses are infrequent and an unmet need exists for novel therapies with distinct mechanisms of action. We investigated the combination of recombinant Interleukin 21 (IL-21), a cytokine with unique immunostimulatory properties, plus sorafenib, a VEGFR tyrosine kinase inhibitor.
Patients and Methods: In this phase 1/2 study, 52 mRCC patients received outpatient treatment with oral sorafenib 400 mg twice daily plus intravenous IL-21 (10-50 mcg/kg) on days 1-5 and 15-19 of each 7-week treatment course. The safety, antitumor activity, pharmacokinetic and pharmacodynamic effects of the combination were evaluated.
Results: In phase 1 (n=19), the maximum tolerated dose for IL-21 with the standard dose of sorafenib was determined to be 30 mcg/kg/day; grade 3 skin rash was the only dose-limiting toxicity. In phase 2, 33 previously-treated patients tolerated the combination therapy well with appropriate dose reductions; toxicities were mostly grade 1 or 2. The objective response rate was 21% and disease control rate was 82%. Two patients have durable responses that are ongoing, despite cessation of both IL-21 and sorafenib, at 41+ and 30+ months, respectively. The median progression-free survival in phase 2 was 5.6 months. The pharmacokinetic and pharmacodynamic properties of IL-21 appeared to be preserved in the presence of sorafenib.
Conclusion: IL-21 plus sorafenib has antitumor activity and acceptable safety in previously treated mRCC patients. IL-21 may represent a suitable immunotherapy in further exploration of combination strategies in mRCC.
"The recent success of cancer immunotherapy has generated exciting hypotheses for its use in combination with other treatment modalities,” stated corresponding author Dr. Shailender Bhatia. “This phase 1/2 study evaluates the combination of cytokine immunotherapy (recombinant Interleukin-21) with a VEGF-targeting tyrosine kinase inhibitor (sorafenib) in patients with advanced renal cell carcinoma."
To read the full article in JITC, click here.
Highly Accessed Article Update
The articles listed below have reached “highly accessed” status in JITC!
Expression of miR-17-92 Enhances Anti-tumor Activity of T-cells Transduced with the Anti-EGFRvIII Chimeric Antigen Receptor in Mice Bearing Human GBM Xenografts
Masasuke Ohno, Takayuki Ohkuri, Akemi Kosaka, Kuniaki Tanahashi, Carl H June, Atsushi Natsume, Hideho Okada Journal for ImmunoTherapy of Cancer 2013, 1:21 (16 December 2013)
Immunologic Responses to Xenogeneic Tyrosinase DNA Vaccine Administered by Electroporation in Patients with Malignant Melanoma
Jianda Yuan, Geoffrey Y Ku, Matthew Adamow, Zhenyu Mu, Sapna Tandon, Drew Hannaman, Paul Chapman, Gary Schwartz, Richard Carvajal, Katherine S Panageas, Alan N Houghton, Jedd D Wolchok Journal for ImmunoTherapy of Cancer 2013, 1:20 (18 November 2013)
Cellular Immunity Induced by a Recombinant Adenovirus- Human Dendritic Cell Vaccine for Melanoma
Naveh HP, Vujanovic L and Butterfield LH Journal for ImmunoTherapy of Cancer 2013, 1:19 (18 November 2013)
Statistical Issues and Challenges in Immuno-oncology
Chen TT Journal for ImmunoTherapy of Cancer 2013, 1:18 (21 October 2013)
Turning T cells on: Epigenetically Enhanced Expression of Effector T-cell Costimulatory Molecules on Irradiated Human Tumor Cells
Kumari A, Cacan E, Greer SF and Garnett-Benson C Journal for ImmunoTherapy of Cancer 2013, 1:17 (23 September 2013)
For additional highly accessed articles, click here.
Members and non-members alike are invited to submit their manuscript in the following categories:
- Basic Tumor Immunology: including 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
Section Editor: Cornelis J.M. Melief, MD, PhD - ISA Therapeutics BV
- Clinical/Translational Cancer Immunotherapy: including first in man clinical trials, phase II/III clinical studies, immune monitoring investigations, tumor microenvironment, host genetics and clinical outcome, updates on clinical trials
Section Editor: F. Stephen Hodi, Jr., MD - Dana-Farber Cancer Institute
- Immunotherapy Biomarkers: including predictive/prognostic biomarker studies, gene expression studies in cancer immunotherapy, serological immune biomarkers, multiparameter flow cytometry-defined immune biomarkers, high content immunohistological studies
Section Editor: Lisa H. Butterfield, PhD - University of Pittsburgh Cancer Institute
- Reviews/Editorials: triggering discussion on hot topics and innovative concepts
Section Editors:
Bernard A. Fox, PhD - Earle A. Chiles Research Institute
Thomas F. Gajewski, MD, PhD - University of Chicago
JITC Editor-in-Chief
Pedro J. Romero, MD - Ludwig Center for Cancer Research
To submit your research visit: www.sitcancer.org/journal
