Vaccination of Patients With Metastatic Renal Cell Carcinoma With Autologous Dendritic Cells Pulsed With Autologous Tumor Antigens in Combination With Interleukin-2: A Phase 1 Study

Oosterwijk-Wakka, J.C.; Tiemessen, Dorien M.; Bleumer, I.; Vries, I. Jolanda M. de; Jongmans, W.; Adema, Gosse J.; Debruyne, F.M.J.; Mulder, P. H. De; Oosterwijk, Egbert; Mulders, Peter F.A.

doi:10.1097/00002371-200211000-00006

Cited by 92 publications

(51 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…36,[39][40][41][42]45 So far, few RCC-associated antigens are known and have been clinically evaluated. 46,[48][49][50][51] We discovered by SSH that MAGE-9, originally described by De Plaen et al, 73 is also expressed in RCC 52 and have explored here its potential as an additional therapeutic target for RCC.…”

Section: Discussionmentioning

confidence: 99%

“…[33][34][35] Cell-mediated immunotherapeutic protocols in RCC have been based on tumor lysate-loaded DCs. [36][37][38][39] Vaccination-induced remissions and an increase in the 5-year survival rate to 70% have been observed. [40][41][42] Application of tumor antigen cDNA 43 or of DC transduced with tumor antigen mRNA or cDNA 44,45 has been reported also to improve survival time, albeit to a minor degree.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Generation of RAGE‐1 and MAGE‐9 peptide‐specific cytotoxic T‐Lymphocyte lines for transfer in patients with renal cell carcinoma

Oehlrich

Devitt

Linnebacher

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

Renal cell carcinomas (RCCs) are supposed to be immunogenic, and several clinical trials of immunotherapy using tumor lysatepulsed dendritic cells (DCs) have been performed. We report on the generation of RAGE-1 and MAGE-9 peptide-specific CTL lines. RAGE-1 and MAGE-9 are expressed in 56% and 38% of RCCs. Seven MAGE-9-and 13 RAGE-1-derived peptides were found to be immunogenic in the context of the HLA-A*0201 MHC. CTLs were generated by coculture with peptide-pulsed, activated B cells, which were easily generated in great quantities and displayed functional activity for a prolonged period of time. MAGE-9 and RAGE-1 peptide-specific CTL lines were strictly peptide-specific and displayed high cytotoxic activity not only against peptide-loaded T2 cells but also against HLA-A*0201-positive RCC lines, which naturally express MAGE-9, RAGE-1 or both. Thus, B cells are well suited as APCs for the generation of large numbers of tumor peptide-specific CTLs for adoptive transfer. MAGE-9 as well as RAGE-1 may well provide suitable targets for immunotherapy of RCC. ' 2005 Wiley-Liss, Inc.Key words: human renal cell carcinoma; antigen-presenting cell; peptide-specific cytotoxic T lymphocyte With 1-2% of solid tumors, RCCs are less frequent than prostate and bladder carcinomas.1 However, the prognosis of patients with RCC is poor as one-third of patients already have metastatic disease at the initial presentation and 30-40% develop distant metastases after resection of the primary tumor.2,3 Median survival time of metastatic RCC is only 6-8 months, and the 5-year survival rate is <5%. As >80% of RCCs express the phenotype of multidrug resistance, chemotherapy is rarely efficient. [4][5][6] However, RCCs are supposed to be immunogenic; 7-11 hence, immunotherapeutic strategies are dominant. should be mentioned. The antibody becomes internalized, 32 and application of 125 I-coupled G250 has been reported to retard tumor progression. 33-35Cell-mediated immunotherapeutic protocols in RCC have been based on tumor lysate-loaded DCs.36-39 Vaccination-induced remissions and an increase in the 5-year survival rate to 70% have been observed. [40][41][42] Application of tumor antigen cDNA 43 or of DC transduced with tumor antigen mRNA or cDNA 44,45 has been reported also to improve survival time, albeit to a minor degree. For antigen-specific vaccination in RCC, 46,47 so far MUC1, HSP96 and MN/CAIX have been used. Yet, the therapeutic efficacy remains below expectation. [48][49][50][51] We previously observed, by SSH, expression of MAGE-9 in RCC.52 As RAGE-1 has been described as an immunogenic RCC-associated antigen, [53][54][55] we explored the frequency of MAGE-9 expression in RCC and identified HLA-A*0201-restricted immunogenic MAGE-9 peptides in comparison to RAGE-1. We also report on the efficacy of B cells in peptide presentation and stimulation of peptide-specific CTLs. Material and methods Tumor linesHuman RCC lines 769-p, 56 Caki-1 and Caki-2, 57 ACHN, KTCTL-28, KTCTL-30, KTCTL-53 and KTCTL-111 (tumor bank,

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Generation of RAGE‐1 and MAGE‐9 peptide‐specific cytotoxic T‐Lymphocyte lines for transfer in patients with renal cell carcinoma

Oehlrich

Devitt

Linnebacher

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…The possibility to generate in vitro functional DCs from peripheral blood monocytes (13)(14)(15)(16) or from CD34 + progenitors obtained from cord blood (17)(18)(19), bone marrow (BM) or cytokine mobilized peripheral blood (20)(21)(22)(23) has opened a new field of vaccine-based immunotherapy for cancer. Thus, various DC-based clinical trials have been performed for treatment of metastatic RCCs using either tumor lysate-pulsed DCs (24)(25)(26), tumor cell-DC hybrids (27)(28)(29), tumor RNA-transfected DCs (30) or more recently DCs loaded with HLA-A2-restricted MUC1-derived peptides (31). These clinical trials performed with monocyte-derived DCs (Mo-DCs) provide evidence of relatively good biological immune anti-tumor responses, but low clinical responses.…”

Section: Introductionmentioning

confidence: 99%

“…Langerhans cells and interstitial dermal-type DC, and seem able to achieve a large immune response (36,37). Interestingly, DC-based immunotherapy can be also combined to IL-2 administration (24,38) or to anti-angiogenic drugs that have recently proven their efficiency in the treatment of advanced RCCs (39).…”

Section: Introductionmentioning

confidence: 99%

Massive expansion of regulatory T-cells following interleukin 2 treatment during a phase I-II dendritic cell-based immunotherapy of metastatic renal cancer

Lemoine¹

2009

Int J Oncol

View full text Add to dashboard Cite

Abstract. Cytotoxic chemotherapy is ineffective in metastatic renal cancer. However, systemic administration of interleukin 2 (IL-2) or infusion of dendritic cells (DCs) loaded with tumor extracts can lead to some response rates with concomitant survival improvements. We report the results of a phase I-II pilot study combining DCs and IL-2 where six patients were included. DCs were derived from bone marrow CD34 + cells and loaded with autologous tumor extracts. CD34-DC vaccines were infused subcutaneously at day 45, 52, 59, 90 and 120 following surgery in combination with IL-2, that was subsequently administrated after the 3rd and 4th DC vaccinations. Preparation of tumor extracts and CD34-DCs were satisfactory in all patients but one. Due to rapid tumor progression, one patient was excluded before vaccination. In the 4 remaining patients, two received 3 vaccinations, while the 2 others received 5 vaccinations and the full IL-2 treatment. No adverse effect due to the vaccinations was observed. A specific immune response against autologous tumor cells was observed in the 2 patients who completed the treatment. Interestingly, these 2 patients had a more prolonged survival than the patients receiving 3 vaccinations. Importantly, a transient and massive increase of circulating natural regulatory T-cells (nTregs) was evidenced in 3 patients following IL-2 administration. Overall, the use of CD34-DC vaccines is feasible, safe and non-toxic. A specific antitumor immune response can be detected. However, our data highlights that IL-2 is a potent inducer of nTregs in vivo and as such may have a negative impact on cancer immunotherapy.

show abstract

“…However, the response rates are low and the toxicity significant. Therefore, new treatment modalities are being studied (Nathan and Eisen, 2002;Oosterwijk-Wakka et al, 2002).…”

mentioning

confidence: 99%

A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients

Bleumer¹,

Knuth²,

Oosterwijk³

et al. 2004

Br J Cancer

158

View full text Add to dashboard Cite

Chimeric monoclonal antibody G250 (WX-G250) binds to a cell surface antigen found on 490% of renal cell carcinoma (RCC). A multicentre phase II study was performed to evaluate the safety and efficacy of WX-G250 in metastatic RCC (mRCC) patients. In all, 36 patients with mRCC were included. WX-G250 was given weekly by intravenous infusion for 12 weeks. Patients with stable disease (SD) or response were eligible to receive additional treatment for 8 weeks. None of the 36 enrolled patients experienced any drug-related grade III or IV toxicity. Only three patients had grade II toxicity possibly related to the study medication. In all, 10 patients had SD and received extended treatment. One complete response and a significant regression was observed during the follow-up of the treatment. Five patients with progressive disease at study entry were stable for more than 6 months after study entry. The median survival after treatment start was 15 months. The weekly schedule of WX-G250 was well tolerated. With a median survival of 15 months after the start of this treatment and two late clinical responses, WX-G250 seems to be able to modulate mRCC. To improve the activity of WX-G250-specific antibody-dependent cellular cytotoxicity and the clinical response rate, currently combinations of WX-G250 with cytokines are in phase II trials.

show abstract

Vaccination of Patients With Metastatic Renal Cell Carcinoma With Autologous Dendritic Cells Pulsed With Autologous Tumor Antigens in Combination With Interleukin-2: A Phase 1 Study

Cited by 92 publications

References 31 publications

Generation of RAGE‐1 and MAGE‐9 peptide‐specific cytotoxic T‐Lymphocyte lines for transfer in patients with renal cell carcinoma

Generation of RAGE‐1 and MAGE‐9 peptide‐specific cytotoxic T‐Lymphocyte lines for transfer in patients with renal cell carcinoma

Massive expansion of regulatory T-cells following interleukin 2 treatment during a phase I-II dendritic cell-based immunotherapy of metastatic renal cancer

A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients

Contact Info

Product

Resources

About