Human tumor cell modification by virus infection: an efficient and safe way to produce cancer vaccine with pleiotropic immune stimulatory properties when using Newcastle disease virus

Schirrmacher, Volker; Haas, C; Bonifer, R; Ahlert, T.; Gerhards, Roswitha; Ertel, C

doi:10.1038/sj.gt.3300787

Cited by 139 publications

(133 citation statements)

References 36 publications

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“…As stimulator cells, we used MCF-7 breast carcinoma cells that were inactivated with 200 Gy g-irradiation via a 137 Cs source (Gammacell 1000, Atomic Energy of Canada, Chalk River, Canada) and then infected with NDV Ulster (100 HU per 10 7 cells) as described. 11 After 3 days incubation in presence or absence of the new bispecific proteins in RPMI-1640 medium plus 10% FCS, the cells were washed and used in the TNA assay described below.…”

Section: Hybridoma and Other Cell Linesmentioning

confidence: 99%

“…Human tumor cell infection by NDV has been shown to be an efficient and safe way to produce cancer vaccine with pleiotropic immune stimulatory properties. 11 Upon infection by NDV, human tumor cells upregulate expression of HLA and cell adhesion molecules, produce interferons and chemokines and finally undergo apoptosis. 12 NDV was also shown to induce TNF-related apoptosis inducing ligand (TRAIL), which can mediate tumoricidal activity.…”

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confidence: 99%

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A tumor vaccine containing anti‐CD3 and anti‐CD28 bispecific antibodies triggers strong and durable antitumor activity in human lymphocytes

Haas

Lulei

Fournier

et al. 2005

Intl Journal of Cancer

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We recently reported on newly designed virus‐targeted bispecific CD3‐ and CD28‐binding molecules for human T‐cell activation. When bound via one arm to a human virus‐modified tumor cell vaccine, these reagents caused a polyclonal T‐cell response and overcame the potential various T‐cell evasion mechanisms of tumor cells. In our current study, we demonstrated the induction of strong antitumor activity in human lymphocytes upon coincubation with a virus‐modified tumor vaccine containing anti‐CD3 and anti‐CD28 bispecific antibodies. Blood mononuclear cells or purified T cells that were coincubated with such a tumor vaccine for 3 days were able to destroy monolayers of human breast carcinoma and other carcinoma cells. Serial transfer to new tumor cell monolayers revealed antitumor cytotoxic activity in such effector cells that lasted for about 10 days. Nontumor target cells appeared to be much less sensitive to the activated effector cells. Although the bispecific molecules alone did not activate effector cells, their binding to virus‐infected tumor cells was important and more effective than their binding to free virus. Antitumor activity of the activated effector cells was mediated through soluble factors as well as through direct cell contact of effector cells with the nontargeted bystander tumor cells. Since the virus‐modified tumor vaccine is well tolerated and already exhibits a certain effectiveness in cancer patients, the combination with new bispecific molecules has the potential to introduce additional antitumor effects. The reagents can also be combined with Newcastle Disease Virus (NDV)‐based oncolytic virotherapy. © 2005 Wiley‐Liss, Inc.

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Section: Hybridoma and Other Cell Linesmentioning

confidence: 99%

mentioning

confidence: 99%

A tumor vaccine containing anti‐CD3 and anti‐CD28 bispecific antibodies triggers strong and durable antitumor activity in human lymphocytes

Haas

Lulei

Fournier

et al. 2005

Intl Journal of Cancer

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“…11 On the basis of these preclinical observations, we subsequently established a similar autologous NDV virus-modified tumor vaccine (ATV-NDV) for human application. 2,12 Recently, we reported results from two non-randomized phase II studies, which aimed at feasibility, safety and clinical benefit. In both studies (glioblastoma multiforme (GBM) 13 and head and neck carcinoma (HNSCC) 14 ), the establishment of primary tumor cell cultures was feasible and successful in about 80-90%.…”

Section: Introductionmentioning

confidence: 99%

“…2 Three cellular mechanisms have been proposed for its anti-neoplastic activities: (i) oncolysis: 3 oncolytic strains may simply kill tumor cells directly. (ii) Provision of danger signals: 4,5 replication of NDV occurs in the tumor cells' cytoplasm.…”

Section: Introductionmentioning

confidence: 99%

Recombinant Newcastle disease virus (NDV) with inserted gene coding for GM-CSF as a new vector for cancer immunogene therapy

Janke

Peeters²,

Leeuw

et al. 2007

Gene Ther

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“…noninfectious in three different assays, thus demonstrating safety. 25 The ATV-NDV vaccine was applied intradermally in clinical phase I and II studies, and the effects of such active specific immunotherapy treatments on postoperative survival were evaluated in high-risk cancer patients. Such vaccinations started in Germany as early as 1988 and now involve several hundred patients.…”

Section: Discussionmentioning

confidence: 99%

An effective strategy of human tumor vaccine modification by coupling bispecific costimulatory molecules

Haas

Herold‐Mende

Gerhards³

et al. 1999

Cancer Gene Ther

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A new, generally applicable procedure is described for the introduction of defined costimulatory molecules into human cancer cells to increase their T-cell stimulatory capacity. The procedure involves infection with Newcastle disease virus to mediate the cell surface binding of costimulatory molecules (e.g., specially designed bispecific antibodies (bsAb)). The modification is independent of tumor cell proliferation and laborious recombinant gene technology and can be applied directly to freshly isolated and ␥-irradiated patient-derived tumor cells as an autologous cancer vaccine. Following the infection of tumor cells with a nonvirulent strain of Newcastle disease virus, the cells are washed and then further modified by coincubation with bsAbs, which attach with one arm to the viral hemagglutinin-neuraminidase (HN) molecule on the infected tumor cells. The second specificity of one bsAb (bs HN ϫ CD28) is directed against CD28 to augment antitumor T-cell responses by selectively channeling positive costimulatory signals via the CD28 pathway. A second bsAb (bs HN ϫ CD3) was produced to deliver T-cell receptor-mediated signals either alone (bsCD3 vaccine) or in combination with anti-CD28 (bsCD3 vaccine plus bsCD28 vaccine). In human T-cell stimulation studies in vitro, the bsCD28 vaccine caused an up-regulation of early (CD69) and late (CD25) T-cell activation markers on CD4 and CD8 T lymphocytes from either normal healthy donors or cancer patients (autologous system) and induced tumor cytostasis in nonmodified bystander tumor cells. In addition, in combination with the bsCD3 vaccine, augmented antitumor cytotoxicity and T-cell proliferative responses were observed. This tumor vaccine modification procedure is highly specific, quick, economic, and has a broad range of clinical applications. T here is now much evidence that an antigen (Ag)-specific, T-cell-mediated immune response requires, apart from the Ag, additional costimulatory signals. 1,2 These signals are normally provided by professional Ag-presenting cells (APCs) such as dendritic cells, macrophages, and activated B lymphocytes but not, for instance, by carcinoma cells, which represent the majority of human tumors and are derived from the non-APCtype cells that form the epithelial layers. In the absence of costimulation, encounters with a tumor-associated Ag (TAA) can lead to T-cell inactivation or death rather than to proliferation and differentiation into effector cells. Modern gene therapy strategies, therefore, aim at transforming carcinoma cells into professional APCs by transfecting genes that code for T-cell costimulatory molecules, such as CD80 (B7-1), 2,3 CD86 (B7-2), and/or cytokines. 4,5 In support of this concept, some nonimmunogenic transplantable tumor cells were shown to become immunogenic after CD80, CD86, and/or cytokine gene transfection, and mice that rejected such transfectants developed systemic protective immunity against the nontransfected tumor. [2][3][4][5][6] B7 transfection, however, often does not suffice to transfer immunogen...

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Human tumor cell modification by virus infection: an efficient and safe way to produce cancer vaccine with pleiotropic immune stimulatory properties when using Newcastle disease virus

Cited by 139 publications

References 36 publications

A tumor vaccine containing anti‐CD3 and anti‐CD28 bispecific antibodies triggers strong and durable antitumor activity in human lymphocytes

A tumor vaccine containing anti‐CD3 and anti‐CD28 bispecific antibodies triggers strong and durable antitumor activity in human lymphocytes

Recombinant Newcastle disease virus (NDV) with inserted gene coding for GM-CSF as a new vector for cancer immunogene therapy

An effective strategy of human tumor vaccine modification by coupling bispecific costimulatory molecules

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