Irradiated Cells from Autologous Tumor Cell Lines as Patient-Specific Vaccine Therapy in 125 Patients with Metastatic Cancer: Induction of Delayed-Type Hypersensitivity to Autologous Tumor is Associated with Improved Survival

Dillman, Robert O.; Beutel, Linda D.; Barth, Neil M.; Leon, Cristina De; OʼConnor, Audrey A.; Depriest, B. S. N. Carol; Nayak, Shankar K.

doi:10.1089/10849780252824073

Cited by 44 publications

(21 citation statements)

References 15 publications

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“…Equally important, the trial also showed the impracticality of using autologous tumor cells as vaccine components, a fact previously demonstrated by us 20 and others. [40][41][42] These findings support further clinical evaluation of vaccines comprised of TGF-b antisense-modified tumor cells in glioma and other tumors associated with systemic immunosuppression related to TGF-b2 secretion, but they also suggest that the use of allogeneic tumor cells may provide a practical alternative to autologous tumor cells.…”

Section: Discussionmentioning

confidence: 63%

Phase I clinical trial of a TGF-β antisense-modified tumor cell vaccine in patients with advanced glioma

et al. 2006

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We performed a phase I clinical trial in grade IV astrocytoma to assess the safety of a whole-cell vaccine comprising autologous tumor cells genetically modified by a transforming growth factor-b2 (TGF-b2) antisense vector. Blocking secretion of the immunosuppressive molecule TGF-b in this manner should inhibit one of the major mechanisms by which tumor cells evade immune surveillance and should lead to clinically effective antitumor immunity. Six patients with progressive WHO grade IV astrocytoma were enrolled in the trial. Patients received 2-7 subcutaneous injections of 5 Â 10 6 -2 Â 10 7 autologous tumor cells per injection. TGF-b2 secretion by the tumor cells used to vaccinate patients was inhibited by 53-98%. Treatment was well tolerated with only low-grade, transient treatment-related toxicities reported. Two patients had partial regressions and two had stable disease following therapy. The overall median survival was 68 weeks. Median survival of the responding patients was 78 weeks, compared to a historic value of 47 weeks for glioma patients treated conventionally. There were indications of humoral and cellular immunity induced by the vaccine. These findings support further clinical evaluation of vaccines comprised of TGF-b antisense-modified tumor cells.

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Section: Discussionmentioning

confidence: 63%

Phase I clinical trial of a TGF-β antisense-modified tumor cell vaccine in patients with advanced glioma

et al. 2006

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“…In October 2007 she enrolled in a randomized phase-II trial (NCT00436930) in which patients receive either the irradiated tumor cell or dendritic cell vaccine products that had previously been described. [1][2][3][4] She was randomized to the dendritic cell vaccine. She underwent a leukopheresis from which dendritic cells were generated, and these were combined with her irradiated tumor cells from her 2 cell lines.…”

Section: Vaccine-induced Cr In Melanoma 555mentioning

confidence: 99%

“…[1][2][3] In 74 patients with metastatic melanoma, who were treated with an irradiated tumor cell vaccine derived from an autologous tumor cell line, a median survival of 20.5 months was observed, and at a median follow-up of 6 years, the 5-year survival was 29%. 2 In a subsequent trial, in 54 patients with metastatic melanoma treated with a patient-specific vaccine consisting of autologous dendritic cells loaded with antigen from the patient's autologous tumor cell line, the median survival was >5 years with a 54% 5-year survival for all-cause mortality at a median follow-up of 4.5 years.…”

Section: Introductionmentioning

confidence: 99%

Durable Complete Response of Refractory, Progressing Metastatic Melanoma After Treatment with a Patient-Specific Vaccine

Dillman

Nanci

Williams

et al. 2010

Cancer Biotherapy and Radiopharmaceuticals

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A patient with metastatic melanoma who experienced a durable complete response after treatment with a patient-specific vaccine has been described in this article. This 59-year-old woman presented with cervical spine metastases and, within the year, had experienced local disease progression and, despite various therapies, metastases to the axilla, rectum, gall bladder, and multiple soft-tissue sites. She had previously received radiation therapy, combination chemotherapy, interleukin-2 plus interferon biotherapy, and gamma knife radiosurgery, and undergone multiple surgical resections. At the time vaccine therapy was initiated, she had multiple, new, measurable, soft-tissue metastases that were increasing in size. She was treated with a vaccine consisting of autologous dendritic cells incubated with irradiated tumor cells from an autologous tumor cell line and suspended in granulocyte-macrophage colony stimulating factor (GM-CSF), with subcutaneous injections once a week for 3 weeks and monthly for 5 months. There was evidence of disease regression by the completion of therapy. A few months later a complete response was documented by radiologic scans, and subsequently reconfirmed at 6-month intervals. She remains in complete remission >2.5 years after starting the vaccine, and >2 years after completing the vaccine, and survives >4 years after her initial presentation with bone, bowel, and lymph node metastases. This is the first time she has been in a complete remission since her initial diagnosis. Patient-specific vaccines can sometimes induce durable complete regression of progressing soft-tissue melanoma metastases.

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“…This is a highly personalized therapy and requires the generation of either short-term cultures or fully characterized cell lines derived from the tumor. This has been attempted in a number of tumors including melanoma [23,24] and sarcoma [25]. This has variable success rates and does pose the question: why should an autologous vaccine elicit an effective immune response by the patient, when the tumor, in situ, did not?…”

Section: Whole-cell Vaccinesmentioning

confidence: 99%

Biomarkers for the Development of Cancer Vaccines

2006

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Irradiated Cells from Autologous Tumor Cell Lines as Patient-Specific Vaccine Therapy in 125 Patients with Metastatic Cancer: Induction of Delayed-Type Hypersensitivity to Autologous Tumor is Associated with Improved Survival

Abstract: This patient-specific, cell culture-derived, autologous tumor cell vaccine induced anti-tumor immune reactivity that was associated with improved survival in patients with advanced cancer.

Cited by 44 publications

References 15 publications

Phase I clinical trial of a TGF-β antisense-modified tumor cell vaccine in patients with advanced glioma

Phase I clinical trial of a TGF-β antisense-modified tumor cell vaccine in patients with advanced glioma

Durable Complete Response of Refractory, Progressing Metastatic Melanoma After Treatment with a Patient-Specific Vaccine

Biomarkers for the Development of Cancer Vaccines

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