Abstracts for the 25th Annual Scientific Meeting of the International ...

J Immunother Volume 33, Number 8, October 2010
Abstracts
that block high avidity T cell trafficking and activation in neuexpressing
tumors. The results of these studies will be discussed. In
addition, data will be presented evaluating these findings in a neoadjuvant
and adjuvant vaccine study in patients with pancreatic
cancer.
References:
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specific CD8+ T cell responses provide human evidence of in
vivo cross-priming by antigen presenting cells in vaccinated
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latent pools of high avidity CD8+ T cells to the antitumor
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3. Laheru D, Lutz E, Burke J, et al. Allogeneic granulocyte macrophage
colony-stimulating factor-secreting tumor immunotherapy
alone or in sequence with cyclophosphamide for
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and immune activation. Cancer Therapy: Clin Can Res. 2008;
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4. Emens LA, Asquith JM, Leatherman JM, et al. Timed
sequential treatment with cyclophosphamide, doxorubicin, and
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II trial of safety, efficacy, and immune activation. Annals of
Surgery. In press.
Tumor Elimination By Depovaxt Cancer Vaccine Platform
is Accompanied by Reduced Regulatory/Suppressor Cell
Infiltration
Mohan Karkada*w, Tara Quinton*, Genevieve Weir*,
Drew Debayz, Sarah LeBlancz, Chris Bowenz, Marc Mansour*.
*Cellular Immunology, Immunovaccine Inc.; w Microbiology and
Immunology, Dalhousie University; zBiodiagnostics, National
Research Council, Halifax, NS, Canada.
A successful cancer vaccine needs to overcome tumor-induced
immune suppression while enhancing protective Type1-biased
tumor-specific immune responses. We have developed a novel
liposome-based vaccine platform called DepoVaxt (DPX) which
increases the potency of peptide-based cancer vaccines and elicits a
strong cytotoxic T cell response. DPX-0907 is a human DPX based
vaccine containing 7 HLA-A2 restricted peptides indicated for
breast, ovarian and prostate cancer which has recently entered
Phase I clinical trials. DPX-0907 has shown effective immune
induction in HLA-A2 transgenic mice, even in the presence
of tumor-induced suppressor cells and cytokines. To investigate
the effect DPX vaccines have on the regulatory cell population,
we examined the induction and distribution of CD4+
CD25+Foxp3+ (Treg) lymphocytes, immune-suppressive cytokine-secreting
Tr1 cells and myeloid derived suppressor cells
(MDSC) using a HPV16 tumor model. C57BL/6 mice bearing
established C3 tumors were immunized with DPX- or emulsionbased
vaccines and regulatory/suppressor cells were examined in
the blood, spleen and tumor tissue using flow cytometry and
fluorescent microscopy. While emulsion-vaccinated mice showed
an increase in Treg cells in both spleen and blood, particularly after
repeat immunizations, mice treated with DPX vaccine showed no
such increase and the levels remained similar to tumor free naı¨ ve
mice. Similarly, MDSC levels were significantly lower in DPXtreated
mice compared to control mice in spleen, blood and also
within the tumor tissue. Production of Tr1-type cytokines IL-10
and TGF-b by CD4+ and CD8+ T cells was significantly
increased in untreated and mice treated with emulsion vaccine
compared to DPX-treated mice. Analysis of tumor infiltrating
T cells revealed DPX vaccinated mice had lower levels of Tregs and
higher levels of CD8+ T cells. Furthermore, C3 tumor bearing
mice vaccinated with a single dose of DPX-based vaccine containing
the H-2Db-restricted HPV16E7 (49 to 57) peptide conjugated
to the universal T helper peptide exhibited compete tumor
regression two weeks later, which was confirmed by MRI scanning.
These findings provide insight into the mechanisms of DepoVaxtbased
cancer vaccines which may prove advantageous for
immunotherapy of immune-suppressed cancer patients.
Proportion of Tregs and Th17 Cells in Peripheral Blood
of Patients with Gynecologic Cancer
Yong-Man Kim, Shin Wha Lee, Dae-Yeon Kim, Jong-Hyeok Kim,
Joo-Hyun Nam, Young-Tak Kim. Department of Obstetrics and
Gynecology, University of Ulsan, Asan Medical Center, Seoul,
Republic of Korea.
Objectives: Regulatory T lymphocytes (Tregs) and T helper type 17
(Th17) cells were known to have a reciprocal function in tumor
microenvironment. However, the proportions of Tregs and Th17
cells have not been identified in gynecologic cancer. The aim of this
study is to investigate and compare the proportions of Tregs and
Th17 cells.
Materials and Methods: Peripheral blood samples were obtained
from 50 patients treated with gynecologic cancer and 16 healthy
donors in Asan Medical Center from July 2009 to October 2009.
Blood samples were stimulated for 4 hours with PMA/ionomycin
according to the manufacturer’s directions (BD) before intracellular
cytokine staining. Cell surfaces were stained with anti CD4
Abs and anti CD25Abs. And then, cells were fixed with fix/perm kit
and intracellularly stained with anti Foxp3 Abs and anti IL-17a
Abs. The phenotype of lymphocytes was analyzed through the flow
cytometry.
Results: Mean age was 50.5 years in cancer patients and 34.8 years
in healthy individuals. Cancer patients were composed with 16
cervical cancer, 15 ovarian cancer, 16 uterine cancer and 3 another
cancer, and they were all at diagnostic states. We observed the
proportion of Tregs and Th17 cells in total CD4+ T lymphocytes.
Proportion of CD4+CD25high+FoxP3+ Tregs was 0.64 ±
0.11% in cancer patients and 0.20 ± 0.06% in healthy individuals(P