Treatment of Kidney Cancer with Autologous Tumor Cell Vaccines of Short-Term Cell Lines Derived from Renal Cell Carcinoma

Dillman, Robert O.; Barth, Neil M.; VanderMolen, Louis A.; Garfield, David H.; Leon, Cristina De; OʼConnor, Audrey A.; Mahdavi, Khosrow; Nayak, Shankar K.

doi:10.1089/108497801750096023

Cited by 17 publications

(7 citation statements)

References 29 publications

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“…Vaccination immunotherapy was applied in patients with metastatic renal cell carcinoma before or after palliative nephrectomy and in most cases as a second or third line systemic therapy. The vaccination therapy was tested in phase I and phase II trials without control groups (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36). The number of patients per trial ranged between 5 and 41 patients.…”

Section: Patients For Vaccinationmentioning

confidence: 99%

Vaccination Immunotherapy — An Update

Doehn

Jocham

2004

Scand J Surg

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Renal cell carcinoma is often regarded as an "immunogenic tumor". Organ-confined tumors are best treated by operative removal. Adjuvant strategies, however, may improve the outcome after operative therapy. Recently, a phase-III trial using an autologous renal tumor cell vaccine was able to demonstrate a reduction of the risk of progression in patients after radical nephrectomy for renal cell carcinoma larger than 2.5 cm. These results were achieved with minimal side effects. Patients with metastases have a poor prognosis. Thirty years ago autologous tumor cell vaccination resulted in remissions in a small number of patients. Almost all vaccination reports focus on patients with metastatic renal cell carcinoma. These reports differ considerably in their modes of preparation, stimulation, application route and intervals and other relevant parameters. More important, clinical response is limited in most studies. For metastatic renal cell carcinoma none of the various vaccination approaches are being currently investigated in phase-III trials. Ongoing efforts focus on development of more powerful vaccines. This review summarizes vaccination approaches for renal cell carcinomas published in the past 4 years.

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Section: Patients For Vaccinationmentioning

confidence: 99%

Vaccination Immunotherapy — An Update

Doehn

Jocham

2004

Scand J Surg

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“…Compared with melanoma studies, efforts to improve outcomes for patients with RCC using GM‐CSF have been disappointing. Antitumor effects of GM‐CSF have been low, with few partial responses, although it was reported that these responses were slightly better in patients who were tumor free at the time of treatment90 and among patients who had not received prior therapy 91. In a recent Phase I trial by de Gast et al, combination therapy for patients with progressive, metastatic RCC with GM‐CSF, IL‐2, and IFN‐γ resulted in significant stimulation of effector cells and complete responses in three of eight patients 92.…”

Section: Antitumor Activity Of Gm‐csf Therapy Alonementioning

confidence: 99%

Modulation of antitumor immune responses by hematopoietic cytokines

Waller¹,

Ernstoff²

2003

Cancer

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BACKGROUNDAdvances in immunotherapy for the treatment of patients with malignant disease have led to increasingly successful use of these methods in the clinical setting. This review presents findings from recent studies that have explored improved methods for the presentation of tumor‐associated antigens and for the restoration of tumor specific immune responses using cytokine therapy.METHODSA review of human clinical trial research on immune cytokines from 1995 (MEDLINE) to the present was conducted. Particular attention was focused on articles that reported results from Phase II or later clinical studies in patients with malignant disease.RESULTSThe defects in cellular immunity commonly seen in patients with malignancies often are expressed as tumor specific anergy. Reversing patient tolerance to tumor antigens may be accomplished by treatment with immunoregulatory cytokines, such as Flt‐3 and granulocyte‐macrophage–colony stimulating factor, that mature and activate dendritic cells. Published clinical studies indicate that granulocyte‐macrophage–colony stimulating factor stimulates antigen‐presenting cells and has promising antitumor activity as an adjunct or as stand‐alone therapy for patients with malignant disease, including leukemia, melanoma, breast carcinoma, prostate carcinoma, and renal cell carcinoma.CONCLUSIONSImmune‐modulating cytokines may be used alone or in combination with other treatments to help restore immune function, improve response to tumor‐associated antigens, and reduce the toxic effects of standard antitumor therapies. The evolving understanding of how dendritic cells regulate immune responses and promising results from published studies of immune‐enhancing cytokines in the treatment of patients with malignant disease support the conduct of randomized clinical trials to confirm the clinical benefit of these immunotherapeutic strategies. Cancer 2003;97:1797–809. © 2003 American Cancer Society.DOI 10.1002/cncr.11247

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“…4,5 For several years, we have been investigating the safety and therapeutic potential of patientspecific autologous vaccines derived from shortterm autologous cell lines. [6][7][8][9][10][11][12] Theoretical advantages for the use of cells from short-term autologous tumor cell lines include: (1) the certainty that one is immunizing with antigens from the patient's own tumor, (2) an unlimited supply of tumor antigen, (3) immunization with the stem cells or progenitor cells from the tumor, (4) immunization with pure tumor cells without contamination from normal cells, (5) presentation of tumor antigens in the context of the cell membrane on metabolically active cells, (6) availability of target cells for in vitro testing of tumorspecific humoral and/or cell-mediated responses before and after vaccination, and (7) the availability of pure tumor cells for patient-specific delayed tumor hypersensitivity skin testing. Such an approach is practical for patients with metastatic melanoma, because regional recurrences and distant metastases are often in sites that are readily accessible to surgical excision, which provides an opportunity to obtain fresh tissue from which to try to establish tumor cell lines.…”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11] We have combined three new strategies in an effort improve on this autologous tumor cell line vaccine approach. Firstly, we, and others, have demonstrated that dendritic cells, believed to be the optimal immune cell for antigen presentation, can be derived consistently from peripheral blood mononuclear cells.…”

Section: Introductionmentioning

confidence: 99%