June 2014 Edition
Below are the abstracts of articles published in this month's issue:
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Strategies for Improving the Reporting of Human Immunophenotypes by Flow Cytometry |
| Gustafson MP, Lin Y, Ryder M and Dietz AB Journal for ImmunoTherapy of Cancer 2014, 2:18 (18 June 2014) |
Background
Flow cytometry is the gold standard for phenotyping and quantifying immune cells. New technologies have greatly increased our capacity to measure both routine and complex immunophenotypes. The reporting of immunophenotype data is not consistent in human studies yet it is quite critical for understanding disease specific changes, responses to immunotherapies, and normal immune homeostasis. Here we examine the barriers that hinder cross comparisons of flow cytometry data collected from human studies and clinical trials.
Findings
We demonstrate that phenotypes reported as percentages within a cell compartment (i.e. myeloid derived suppressor cells as a percent of mononuclear cells) without providing data on the parent population may contribute to misleading conclusions. The enumeration of phenotypes as cell counts (cells/μl) provides a basis to more accurately compare the relationships among phenotypes. Finally, we provide evidence that density gradient centrifugation, which eliminates the ability to measure phenotypes as cell counts, can affect the expression of surface markers and consequently alter the distribution of particular immunophenotypes.
Conclusions
We propose that by measuring immunophenotypes as cell counts from minimally manipulated samples (whole blood) will improve the reporting of flow data and facilitate more direct comparisons of data across human studies.
From the Authors
“There is tremendous variability in the way in which flow cytometry data is collected and analyzed in human research studies. Therefore, the standardization of measurements and assessments of immunophenotypic data is critical for the advancement of novel immunotherapeutics," said Dr. Michael P. Gustafson. "We provide data indicating how common approaches to flow can provide difficult to interpret data, and a method to improve the standardization of flow cytometry to facilitate better inter-laboratory comparisons and subsequently improve the translational impact of clinical research.”
To access the full article, please click here.
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A Phase 2, Single-Arm Study of an Autologous Dendritic Cell Treatment Against Mucin 1 in Patients with Advanced Epithelial Ovarian Cancer |
| Mitchell PLR, Quinn MA, Grant PT, Allen DG, Jobling TW, White SC, Zhao A, Karanikas V et al. Journal for ImmunoTherapy of Cancer 2014, 2:16 (18 June 2014) |
Background
Mucin 1 antigen, highly expressed by epithelial ovarian cancer (EOC), is a potential target for immunotherapy. A previous successful phase 1 trial was conducted in patients with adenocarcinoma who were injected with autologous monocyte-derived dendritic cells (DCs) incubated with mannanosylated mucin 1 protein (M-FP). The present study was a phase 2 trial of Cvac in patients with advanced EOC.
Methods
Eligible patients had EOC with progressive disease, defined as an increase in CA125 of ≥ 25% in 1 month. The primary endpoint was CA125 response or stabilization. Peripheral blood mononuclear cells were collected by leukapheresis and cultured to generate DCs. The DC were incubated with M-FP, and after washing were prepared for injection into the patient intradermally every 4 weeks for 3 doses, then every 10 weeks for up to 12 months.
Results
All 28 patients recruited were evaluable for safety and 26 for efficacy. All had undergone surgery and platinum-based chemotherapy, and 57% of patients received ≥ 3 chemotherapy regimens. There were no Grade 3 or 4 toxicities considered related to Cvac. Four patients showed CA125 response or stabilization (2 patients with major responses, 1 minor response, 1 stabilization) of median duration 10.3 months (5.3–16.3 months). An additional patient had > 25% CA125 reduction (not confirmed).
Conclusions
Cvac immunotherapy was well tolerated. Clinical activity in EOC was evident based on decline or stabilization of CA125 in some patients, supporting ongoing development of Cvac in ovarian carcinoma and planning of additional trials of patients in remission are currently underway.
From the Authors
“CVac is an autologous dendritic cell therapy that targets mucin 1-expressing cancers and is administered as an intradermal injection. In a phase 2 trial of patients with progressive advanced ovarian cancer, CVac slowed the rate of disease progression in some patients, without significant toxicity. Further studies have now moved to the minimal residual disease setting, with a phase 2 trial commenced in ovarian cancer.”
To access the full article, please click here.
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Opportunistic Infections in Patients Treated with Immunotherapy for Cancer |
| Kyi C, Hellmann MD, Wolchok JD, Chapman PB and Postow MA Journal for ImmunoTherapy of Cancer 2014, 2:19 (18 June 2014) |
Full Abstract
Immunomodulatory antibodies that enhance the immune system to fight cancer are revolutionizing the treatment of patients with an expanding variety of malignancies. There is a unique spectrum of side effects associated with immunomodulatory antibodies, termed immune-related adverse events (irAEs), which include colitis and hepatitis among others. The treatment of refractory or severe irAEs can occasionally require significant immunosuppression, involving steroids or tumor necrosis factor-alpha antagonists, placing these patients at risk for infections. We present the first reported case to our knowledge of an opportunistic infection in a patient treated with an immunomodulatory antibody. As the use of immunomodulatory antibodies expands and more patients develop irAEs that require treatment with immunosuppression, recognition of the potential for opportunistic infections in this emerging patient population will be critical. Prospective trials are needed to define the optimal immunosuppressive management of irAEs and determine whether prophylactic antiviral, antibacterial, or antifungal therapies are beneficial in this unique population.
From the Authors
“Immunotherapy has demonstrated remarkable recent success in the treatment of patients with a variety of cancers," said Dr. Michael Postow. "Nevertheless, inflammatory side effects often necessitate immunosuppressive treatments which place this emerging patient population at risk for opportunistic or rare infections. Awareness of this possibility and prompt diagnosis and treatment may help maintain the best patient outcomes.”
To access the full article, please click here.
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Optimizing Immune-Related Tumor Response Assessment: Does Reducing the Number of Lesions Impact Response Assessment in Melanoma Patients Treated with Ipilimumab? |
| Nishino M, Gargano M, Suda M, Ramaiya NH and Hodi FS Journal for ImmunoTherapy of Cancer 2014, 2:17 (18 June 2014) |
Background
Investigate the impact of the reduction of the number of target lesions on immune-related response assessment in advanced melanoma patients treated with ipilimumab.
Method
Ninety patients (53 males, 37 females; age range: 25–87) with advanced melanoma treated with ipilimumab in two clinical trials were studied. Tumor measurements during trial allowing up to 5 lesions per organ and 10 lesions in total were retrospectively reviewed. A second set of tumor measurements allowing up to 2 lesions per organ and 5 lesions in total was generated. Immune-related response assessments by two measurements were compared.
Results
The number of target lesions was significantly reduced when up to 2 per organ and 5 in total lesions were allowed (Wilcoxon P < 0.0001). The immune-related response assessment using reduced number of lesions was highly concordant with assessment using the original number of lesions (Spearman r for the percent change on 1st-3rd follow-up: 0.860-0.970; κw for best immune-related response: 0.908). Median time-to-progression was 26.9 months (95%CI: 9.1-∞) by both assessments. Interobserver agreement of measurements was high for both assessments, with the concordance correlation coefficient above 0.98.
Conclusion
Reduction of the number of target lesions did not significantly affect immune-related response assessment or the measurement variability in advanced melanoma patients treated with ipilimumab. Using up to 2 per organ and 5 in total target lesions is proposed to assess immune-related response, while it is important to keep other novel features of immunerelated response criteria such as confirmation of progression and inclusion of new lesion measurements.
From the Authors
“Given the rapidly expanding role of cancer immunotherapy, establishing a strategy to accurately characterize immune-related tumor response is critically important. Having previously shown that the unidimensional irRC is highly concordant with the bidimensional irRC [Clin Cancer Res. 2013;19:3936-43], we took one step forward and demonstrated that up to 2 lesions per organ and 5 lesions in total (as in RECIST1.1) were sufficient for immune-related response assessment," said Dr. Mizuki Nishino. "The knowledge obtained from the present study contributes to optimize trial designs and response assessment in cancer immunotherapy. Authors believe that systematic radiologic investigations during immunotherapy help to lead the community toward developing a “common language” to best describe the results of cancer immunotherapy.”
To access the full article, please click here.
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Implementation of an Interleukin-2 National Registry: an Opportunity to Improve Cancer Outcomes |
| Wong MK, Kaufman HL, Daniels GA, McDermott DF, Aung S, Lowder JN and Morse MA Journal for ImmunoTherapy of Cancer 2014, 2:20 (18 June 2014) |
Full Abstract
Cancer registries have proven valuable with respect to validating therapeutic safety and drug efficacy, uncovering real-world implementation practices, and their evolution over time. Modern cancer therapeutics are approved as single agents oftentimes compared to the least active approved standard agent in randomized trials. However, the burgeoning diversity and number of drugs introduces a complexity that quickly outstrips the knowledge provided by these pivotal trials. This gap in information is particularly relevant when survival is the primary therapeutic endpoint. In addition, the inherent complexity of the immune response will make registries a particularly important tool in expeditiously understanding solid tumor immunotherapy and patient outcomes.
From the Authors
“There have been significant advances in tumor immunotherapy and providing guidance for best clinical practices is a priority. Interleukin-2 induces durable response rates in patients with metastatic renal cell carcinoma and melanoma," said Dr. Howard Kaufman. "A national registry with clinical data from experienced institutions is providing new insights into clinical outcomes, toxicity management and quality patient care. The registry should serve as a model for other immunotherapy agents on the horizon to optimize the potential benefit of these promising new approaches.”
To access the full article, please click here.
Highly Accessed Article Update
Below are the highly accessed research articles published in the month of May:
Tumor Immunology and Cancer Immunotherapy: Summary of the 2013 SITC Primer
Raval RR, Sharabi AB, Walker AJ, Drake CG and Sharma P
Journal for ImmunoTherapy of Cancer 2014, 2:14 (14 May 2014)
Durable Responses and Reversible Toxicity of High-Dose Interleukin-2 Treatment of Melanoma and Renal Cancer in a Community Hospital Biotherapy Program
Payne R, Glenn L, Hoen H, Richards B, Smith JW, Lufkin R, Crocenzi TS, Urba WJ et al.
Journal for ImmunoTherapy of Cancer 2014, 2:13 (14 May 2014)
Cytokine Responsiveness of CD8+ T Cells is a Reproducible Biomarker for the Clinical Efficacy of Dendritic Cell Vaccination in Glioblastoma Patients
Everson RG, Jin RM, Wang X, Safaee M, Scharnweber R, Lisiero DN, Soto H, Liau LM et al.
Journal for ImmunoTherapy of Cancer 2014, 2:10 (13 May 2014)
Submit You Manuscript to Win a Best Paper Award!
The JITC Best Clinical Application Paper and the JITC Best Basic Science Paper Award 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 multiple Society outlets and networks.
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
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 through 2014 (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
