Immunogenicity and safety profiles of genetic vaccines against human Her-2/neu in cynomolgus monkeys

Ko, Hyun‐Jeong; Kim, Yoon Jun; Kim, Yong Soo; Jm, Kim; Ho, SH; Jeong, Joo‐Won; Sh, Oh; Ja, Chae; Cy, Kim; Lee, PS; Kang, C. Yong

doi:10.1038/gt.2008.81

Cited by 4 publications

(2 citation statements)

References 36 publications

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“…centrifugation step at room temperature, and the cells were subsequently incubated for an additional 18 h. In some experiments, KBC009 was loaded into the prepared B cells for NKT activation, based on our previous studies. 6,10,45 Quantitative real-time PCR Total RNA was isolated by an RNeasy Mini Kit (Qiagen, Valencia, CA, USA) and then reverse-transcribed using amfiRivert Platinum (GenDEPOT, Baker, TX, USA). Quantitative real-time PCR was performed on a LightCycler optical system (Roche, Basel, Switzerland) and SYBR Premix Ex Taq (Takara, Otsu, Japan).…”

Section: B-cell Isolation and B-cell-based Vaccine Preparationmentioning

confidence: 99%

Enhanced antitumor immunotherapeutic effect of B-cell-based vaccine transduced with modified adenoviral vector containing type 35 fiber structures

Kim¹,

Seo²,

Chae³

et al. 2013

Gene Ther

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For successful clinical tumor immunotherapy outcomes, strong immune responses against tumor antigens must be generated. Cell-based vaccines compromise one strategy with which to induce appropriate strong immune responses. Previously, we established a natural killer T-cell (NKT) ligand-loaded, adenoviral vector-transduced B-cell-based anticancer cellular vaccine. To enhance tumor antigen delivery to B cells, we established a modified adenoviral vector (Ad-k35) that encoded a truncated form of the breast cancer antigen Her2/neu (Ad-k35HM) in which fiber structure was substituted with adenovirus serotype 35. We observed increased tumor antigen expression with Ad-k35HM in both human and murine B cells. In addition, an Ad-k35HM-transduced B-cell vaccine elicited strong antigen-specific cellular and humoral immune responses that were further enhanced with the additional loading of soluble NKT ligand KBC009. An Ad-k35HM-transduced, KBC009-loaded B-cell vaccine efficiently suppressed the in vivo growth of established tumors in a mouse model. Moreover, the vaccine elicited human leukocyte antigen (HLA)-A2 epitope-specific cytotoxic T-cell responses in B6.Cg (CB)-Tg (HLA-A/H2-D) 2Enge/Jat mice. These findings indicated that the Ad-k35 could be appropriate for the preclinical and clinical development of B-cell-based anticancer immunotherapies.

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Section: B-cell Isolation and B-cell-based Vaccine Preparationmentioning

confidence: 99%

Enhanced antitumor immunotherapeutic effect of B-cell-based vaccine transduced with modified adenoviral vector containing type 35 fiber structures

Kim¹,

Seo²,

Chae³

et al. 2013

Gene Ther

Self Cite

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“… 12 When a heterologous prime-boost vaccination scheme involving a plasmid (pHM-GM-CSF) and an adenoviral vector (Ad-HM) encoding only HM was applied to nonhuman primates, similar observations were made regarding safety as well as immune induction. 13 As adjuvant, GM-CSF was selected among interleukin (IL)-12, IL-15, IL-18, osteopontin (Eta)-1, and Fms-like tyrosine kinase-3 ligand (Flt-3L) because it induced higher HER2-specific cellular immune response and reduced the tumor sizes in tumor-bearing murine. 12 …”

Section: Introductionmentioning

confidence: 99%

A phase 1 study of a heterologous prime-boost vaccination involving a truncated HER2 sequence in patients with HER2-expressing breast cancer

Kim

Ahn

Kim

et al. 2015

Molecular Therapy - Methods & Clinical Development

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A phase 1 clinical trial was conducted to assess the safety, tolerability, and preliminary efficacy of a heterologous prime-boost strategy involving plasmid DNA (pHM-GM-CSF, expressing truncated human epidermal growth factor receptor 2 (HER2) and granulocyte macrophage colony-stimulation factor (GM-CSF) as a bicistronic message) and an adenoviral vector (Ad-HM, containing the same modified HER2 sequence only), in patients with stage III–IV metastatic breast cancer expressing HER2. Nine eligible subjects were divided into three cohorts based on the dosages (2, 4, and 8 mg/patient/visit) of pHM-GM-CSF used as the primer, which was intramuscularly injected three times at weeks 0, 2, and 4. It was followed by a single injection of Ad-HM (3 × 109 virus particles), used as a booster, at week 6. During the 6-month follow-up period, adverse events (AEs), pharmacokinetics and pharmacodynamics, and HER2-specific cellular and humoral immune responses were evaluated. Seven cases of minor grade 1 toxicities in four of nine subjects and no serious drug-related AEs were reported. HER2-specific cell-mediated or humoral immunity was produced in all (100%) or three subjects (33%), respectively. One subject showed a partial response, and seven subjects had stable diseases. However, there were no differences in clinical tumor response and HER2-specific immune responses among the cohorts. These results showed that intramuscular injections of pHM-GM-CSF and Ad-HM were well tolerated and safe.

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Non-clinical immuno-toxicological evaluation of HER1 cancer vaccine in non-human primates: a 12-month study

Barro¹,

Rivero

Goñi³

et al. 2012

Vaccine

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Immunogenicity and safety profiles of genetic vaccines against human Her-2/neu in cynomolgus monkeys

Cited by 4 publications

References 36 publications

Enhanced antitumor immunotherapeutic effect of B-cell-based vaccine transduced with modified adenoviral vector containing type 35 fiber structures

Enhanced antitumor immunotherapeutic effect of B-cell-based vaccine transduced with modified adenoviral vector containing type 35 fiber structures

A phase 1 study of a heterologous prime-boost vaccination involving a truncated HER2 sequence in patients with HER2-expressing breast cancer

Non-clinical immuno-toxicological evaluation of HER1 cancer vaccine in non-human primates: a 12-month study

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