Active Immunization of Metastatic Melanoma Patients with Interleukin-4 Transduced, Allogeneic Melanoma Cells. A Phase I–II Study. University of Turin, Italy

Cascinelli, Natale; Foà, Robert; Parmiani, Giorgio; Arienti, Flavio; Belli, Filiberto; Bernengo, M. G.; Clemente, Claudio; Colombo, Mario P.; Guarini, Anna; Illeni, Maria Teresa; Mascheroni, Luigi; Melani, Cecilia; Prada, A.; Sulé-Suso, Josep

doi:10.1089/hum.1994.5.8-1059

Cited by 27 publications

(10 citation statements)

References 1 publication

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“…Cells were fixed with 4% formaldehyde in PBS for at least 10 min at 4°C. Fixed cells were then washed twice with complete PBS and filtered X-gal stain (100 mm sodium phosphate pH 7.3(77 mm Na 2 HPO 4 , 23 mm NaH 2 PO 4 ), 1.3 mm MgCl 2 , 3 mm K 3 Fe(CN) 6 , 3 mm K 4 Fe(CN) 6 and 1 mg/ml X-gal) was added. Cells were incubated at 37°C overnight.…”

Section: ␤-Galactosidase Histochemical Assaymentioning

confidence: 99%

“…[3][4][5][6] In contrast to tumours of histological types often associated with relatively high levels of intrinsic immunogenicity, such as melanoma, 7 colorectal cancer is often considered to be less immunogenic and, therefore, less amenable to vaccination approaches. However, since deaths due to colorectal cancer in the USA in 1996 were expected to exceed 54 000, whereas melanoma was expected to kill 7 300 people, it would be of great value if effective immunotherapies for this disease could be developed.…”

Section: Introductionmentioning

confidence: 99%

“…The majority of ex vivo vaccines have so far been prepared using retroviral transduction to generate stably expressing cell populations with integrated vectors. [3][4][5][6] However, even without the need for selection of infected cells, 35 the requirement of retroviral vectors for target cell division still requires medium-term culture of tumour cells following surgery. In contrast, higher efficiency vector systems might remove the need for integration into the target cells because high levels of transient expression should be sufficient to activate the immune system in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Rapid adenoviral transduction of freshly resected tumour explants with therapeutically useful genes provides a rationale for genetic immunotherapy for colorectal cancer

Díaz

Todryk²,

Chong³

et al. 1998

Gene Ther

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To develop protocols for the molecular immunotherapy of can reproducibly be explanted and established in shortcolorectal cancer, we compared the efficacy of three separterm culture. Finally, a rapid transduction protocol has ate classes of therapeutic genes to induce antitumour been developed by which, using adenoviral vectors, as responses in a murine colorectal cell model. Thus, the many as 90% of the cells in these fresh tumour explants effects of two cytokines (IL-2 and GM-CSF) were comcan be engineered to express high levels of the clinically pared with those of a costimulatory gene (B7.1) and a suicrelevant genes (GM-CSF or IL-2) within 1-2 weeks of suride gene (HSVtk). The rank order of efficacy against prigery. Adenovirus-mediated gene delivery was reproducibly mary tumour growth was HSVtk[GCV], B7.1 Ͼ puro, IL-2 and significantly more efficient than retroviral transduction ϾGM-CSF, neo whereas the order of efficacy in inducing using the MFG-␤-Gal retroviral vector over the time-frame antitumour immunity was GM-CSF, IL-2, ϾB7.1, of importance for vaccination. Hence, combination of the HSVtk[GCV]Ͼ puro, neo in a prophylactic vaccination animal model data with the ex vivo modification protocol model. To exploit these data in a clinically relevant and suggests that vaccination of colorectal patients of the realistic way, we also demonstrated that colorectal tumours appropriate stage will be possible and effective.

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Section: ␤-Galactosidase Histochemical Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Rapid adenoviral transduction of freshly resected tumour explants with therapeutically useful genes provides a rationale for genetic immunotherapy for colorectal cancer

Díaz

Todryk²,

Chong³

et al. 1998

Gene Ther

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“…Perhaps the most promising is the introduction of cytokine genes such as interleukin 2 or interleukin 4 [42,43].…”

Section: Whole-cell Polyvalent Vaccinesmentioning

confidence: 99%

Update on active specific immunotherapy with melanoma vaccines

Conforti¹,

Ollila²,

Kelley³

et al. 1997

J. Surg. Oncol.

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“…One potential application of such modified cells to the treatment of human disease is the injection of patient tumour cells, genetically engineered following primary tumour excision, to stimulate the patient anti-tumour response and lead to the eradication of metastases. Indeed, a number of clinical trials have now been initiated in melanoma patients including either vaccination with irradiated autologous melanoma cells secreting IL-2 [27][28][29], with similar cells secreting GM-CSF [30], with allogeneic tumour cells producing IL-4 [31] and with an allogeneic melanoma cell line expressing specific melanoma antigens in association with HLA-A1 and A2 molecules [32], or intratumoural injection of the gene encoding HLA-B7 [33].…”

Section: Introductionmentioning

confidence: 99%

IL-12 stimulation but not B7 expression increases melanoma killing by patient cytotoxic T lymphocytes (CTL)

Wit

Flemming

Harris

et al. 1996

Clinical and Experimental Immunology

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SUMMARYRecent studies have demonstrated that rodent tumour cells engineered to secrete a variety of cytokines, or to express foreign antigens, MHC molecules or co-stimulatory molecules, are rejected by syngeneic animals. These observations have led to the initiation of a number of clinical trials using genetically modified tumour cells, to attempt to stimulate a patient anti-tumour immune response. In this study, a protocol has been developed to test in vitro the specific cytotoxic anti-tumour response generated from melanoma patient lymphocytes. The results showed that IL-12 in combination with IL-2 enhanced the autologous anti-melanoma CTL response, whereas B7.1 antigen expression on tumour cells did not increase anti-melanoma CTL generation. This method could be used to design more appropriate genetically modified tumour vaccines.

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Active Immunization of Metastatic Melanoma Patients with Interleukin-4 Transduced, Allogeneic Melanoma Cells. A Phase I–II Study. University of Turin, Italy

Cited by 27 publications

References 1 publication

Rapid adenoviral transduction of freshly resected tumour explants with therapeutically useful genes provides a rationale for genetic immunotherapy for colorectal cancer

Rapid adenoviral transduction of freshly resected tumour explants with therapeutically useful genes provides a rationale for genetic immunotherapy for colorectal cancer

Update on active specific immunotherapy with melanoma vaccines

IL-12 stimulation but not B7 expression increases melanoma killing by patient cytotoxic T lymphocytes (CTL)

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