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Review
. 2014 Feb 10:8:27-38.
doi: 10.2147/BTT.S55196. eCollection 2014.

Therapeutic vaccines and cancer: focus on DPX-0907

Mohan Karkada  1 , Neil L Berinstein  2 , Marc Mansour  3
Affiliations
Review

Therapeutic vaccines and cancer: focus on DPX-0907

Mohan Karkada et al. Biologics. .

Abstract

In an attempt to significantly enhance immunogenicity of peptide cancer vaccines, we developed a novel non-emulsion depot-forming vaccine platform called DepoVax™ (DPX). Human leukocyte antigen (HLA)-A2 restricted peptides naturally presented by cancer cells were used as antigens to create a therapeutic cancer vaccine, DPX-0907. In a phase I clinical study, the safety and immune-activating potential of DPX-0907 in advanced-stage breast, ovarian, and prostate cancer patients were examined, following encouraging results in HLA-A2 transgenic mice. The DPX-0907 vaccine was shown to be safe and well tolerated, with injection-site reactions being the most commonly reported adverse event. Vaccinated cancer patients exhibited a 61% immune response rate, with higher response rates in the breast and ovarian cancer patient cohorts. In keeping with the higher immune efficacy of this vaccine platform, antigen-specific responses were detected in 73% of immune responders after just one vaccination. In 83% of responders, peptide-specific T-cells were detected at two or more time points post-vaccination, with 64% of these patients showing evidence of immune persistence. Immune monitoring also demonstrated the generation of antigen-specific T-cell memory, with the ability to secrete multiple type 1 cytokines. The novel DPX formulation promotes multifunctional effector/memory responses to peptide-based tumor-associated antigens. The data support the capacity of DPX-0907 to elicit type-1 biased immune responses, warranting further clinical development of the vaccine. In this review, we discuss the rationale for developing DPX-based therapeutic cancer vaccine(s), with a focus on DPX-0907, aimed at inducing efficient anti-tumor immunity that may eventually be shown to prolong patient survival.

Keywords: DPX-0907; DepoVax™; cancer vaccine; immunotherapy.

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Figures

Figure 1
Figure 1
Intracellular IFN-γ in CD8+ T-cells (A) and IFN-γ producing cells (B and C) from draining LNs of HLA-A2 transgenic mice immunized with single- (A and B) or three-dose (C) vaccination, either in DPX-0907 or conventional emulsion vaccine. Draining LN cells from naïve and vaccinated mice were incubated with either unloaded or peptide-loaded DC and stained by intracellular immunofluorescence or in a DC-ELISPOT assay for detecting induction of IFN-γ. Notes: *P<0.01, DPX-0907 versus conventional emulsion vaccine; +P=0.02, single dose versus three doses of conventional emulsion vaccine. Abbreviations: CD, cluster of differentiation; DC, dendritic cell; DPX, DepoVax™; ELISPOT, enzyme-linked immunospot; GM-CSF, granulocyte macrophage colony-stimulating factor; HLA, human leukocyte antigen; IFN, interferon; LN, lymph node; SFU, spot-forming unit.
Figure 2
Figure 2
CD4+IL-10+ cells from spleen and CD4+IFN-γ+ cells from draining LNs of mice immunized with three doses of DPX-0907, oil emulsion vaccine or naïve mice. Splenocytes and LN cells from indicated groups of mice were isolated and activated for 48 hours in the presence of peptides and used for staining to detect suppressor Tr1 and effector CD4 T-cells. Notes: *P=0.03, DPX-0907 versus conventional emulsion vaccine. Abbreviations: CD, cluster of differentiation; DPX, DepoVax™; IFN, interferon; IL, interleukin; LN, lymph node.
Figure 3
Figure 3
Outline of clinical protocol followed in DPX-0907 trial with details on the time-line for screening, treatment and follow-up of late-stage breast, ovarian, and prostate cancer patients. Blood collected at the indicated time points are used for immune monitoring, and the samples up to study day 73 are analyzed. Abbreviations: DPX, DepoVax™; F/U, follow-up; N, number.
Figure 4
Figure 4
DPX-0907-induced increase in the frequency of antigen-specific CD8+ T-cells in vaccinated ovarian, prostate, and breast cancer patients. Patient PBMC were stimulated with indicated peptides for 10 days and were stained with corresponding MHC-multimer reagents to detect CD8+ T-cells with peptide-specific TCR repertoire. HIV-multimer served as a negative control and CMV-specific multimer was used on a known CMV-positive donor PBMC as internal positive control for the assay (data not shown). Notes: Data represent percentage of live gated CD3+CD8+ T-cells that were positive for MHC-multimer staining. Abbreviations: CD, cluster of differentiation; CMV, cytomegalovirus; DPX, DepoVax™; HIV, human immunodeficiency virus; MHC, major histocompatibility complex; PBMC, peripheral blood mononuclear cells; TCR, T-cell receptor; ID, identification number; SD, study day.
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References

    1. Kantoff PW, Higano CS, Shore ND, et al. IMPACT Study Investigators Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411–422. - PubMed
    1. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–723. - PMC - PubMed
    1. Klebanoff CA, Gattinoni L, Restifo NP. CD8+ T-cell memory in tumor immunology and immunotherapy. Immunol Rev. 2006;211:214–224. - PMC - PubMed
    1. Perret R, Ronchese F. Memory T cells in cancer immunotherapy: which CD8 T-cell population provides the best protection against tumours? Tissue Antigens. 2008;72(3):187–194. - PubMed
    1. Gattinoni L, Klebanoff CA, Restifo NP. Paths to stemness: building the ultimate antitumour T cell. Nat Rev Cancer. 2012;12(10):671–684. - PMC - PubMed