New Research Articles Published in the November
Edition of the Journal for ImmunoTherapy of Cancer
Cellular Immunity Induced by a Recombinant Adenovirus- Human Dendritic Cell Vaccine for Melanoma
Hadas Prag Naveh, Lazar Vujanovic, Lisa H Butterfield
Journal for ImmunoTherapy of Cancer 2013, 1:19 (18 November 2013)
Background
Human Adenoviral vectors (HAdV) are immunogenic vectors which have been tested in many vaccination and gene therapy settings. Dendritic cells (DC) transduced by genetically engineered HAdV-5 (HAdV-5/DC), are investigational cancer vaccines being tested clinically. We have previously examined immune responses to HAdV-5 -encoded melanoma tumor antigens. Here, we determined whether the HAdV-5/DC also present immunogenic HAdV-5 vector-derived antigens, and characterized the cellular immune response to the viral as well as encoded melanoma tumor antigens.
Methods
Both CD4+ and CD8+ HAdV-5-specific T cell responses were examined in vitro, with cells from both 8 healthy donors (HD) and 2 melanoma patients. PBMC were stimulated weekly with HAdV-5/DC and responses were examined after each stimulation. We also tested HAdV-5 neutralizing antibody levels and natural killer (NK) cell along with regulatory T cell (Treg) activation and expansion in vitro.
"Human beings are exposed to wild-type adenoviruses in the environment, and adenoviral vectors have been used in several therapeutic settings, for gene therapy, direct injection and by ex vivo transduction of other cells," Lisa H. Butterfield, PhD, corresponding author on the paper, said. "We have used these vectors to engineer dendritic cells to express tumor antigens, but haven't known whether the anti-adenoviral immunity generated at the same time was a positive or negative aspect of this approach. Here, we've learned that there are substantial memory T cells to the virus, regardless of neutralizing antibody titer, and that these cells secrete type 1 cytokines that may help support the anti-tumor antigen immune response."
Click here to read the full abstract and article in JITC.
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)
Background
Prior studies show that intramuscular injection and particle-mediated epidermal delivery of xenogeneic melanosomal antigens (tyrosinase or Tyr, gp100) induce CD8+ T cell responses to the syngeneic protein. To further define the optimal vaccination strategy, we conducted a phase I study of in vivo electroporation (EP) of a murine Tyr DNA vaccine (pINGmuTyr) in malignant melanoma patients.
Methods
Human leukocyte antigen (HLA)-A1, A2, A24 or B35 stage IIb-IV melanoma patients received up to five doses of the mouse tyrosinase DNA vaccine by EP every three weeks at dose levels of 0.2 mg, 0.5 mg, or 1.5 mg per injection. Peripheral blood mononuclear cells (PBMC) were collected, cultured with a peptide pool containing eight HLA class I-restricted Tyr-specific T-cell epitopes, and analyzed by HLA-A*0101-restricted tetramers and intracellular cytokine staining (ICS).
"The study shows that in vivo electroporation with xenogeneic antigens is a feasible means to induce response to self targets," Jedd D. Wolchok, MD, PhD, corresponding author on the paper, said. "It also highlights the possibility of intermolecular epitope spreading as a consequence of successful immunization."
Click here to read the full abstract and article in JITC.
Submit Your Research to JITC!
JITC is an open access, peer-reviewed journal that encompasses all aspects of tumor immunology and cancer immunotherapy, from basic research to clinical applications. Through December 2013, SITC is offering its members free article processing charges, a $2,230 USD value! JITC is accepting submissions from both SITC members and non-members alike in the categories below. For more information and to submit your manuscript visit: www.sitcancer.org/journal.
- Basic Tumor Immunology
Section Editor: Cornelis J.M. Melief, MD, PhD, ISA Therapeutics BV - Clinical/Translational Cancer Immunotherapy
Section Editor: F. Stephen Hodi, Jr., MD, Dana-Farber Cancer Institute - Immunotherapy Biomarkers
Section Editor: Lisa H. Butterfield, PhD, University of Pittsburgh Cancer Institute - Reviews/Editorials
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
Additional Reminder!
Early Registration for SITC's "Advances in Cancer Immunotherapy"
Regional Programs Ends Tonight!
These CME-certified programs provide an understanding of basic immunology principles underlying the clinical application of immunotherapy, provide insights into the indications and clinical management of patients receiving tumor immunotherapy, and discuss emerging drugs and concepts in the tumor immunotherapy field.
Early registration ends tonight, Monday, November 18 at 11:59 pm PST. To register and for program-specific information, click on the links below.
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