Induction of antigen specific cellular immunity by vaccination with peptides from MN/CA IX in renal cell carcinoma

Shimizu, Kazuhiro; Uemura, Hirotsugu; Yoshikawa, Motokiyo; Yoshida, Katsunori; Hirao, Yoshihiko; Iwashima, Kumiko; Saga, Shinsuke; Yoshikawa, Kazuhiro

doi:10.3892/or.10.5.1307

Cited by 13 publications

(27 citation statements)

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“…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. The well-known RCC-associated RAGE-1 [53][54][55] served as a reference antigen.…”

Section: Discussionmentioning

confidence: 99%

“…Yet, the therapeutic efficacy remains below expectation. [48][49][50][51] We previously observed, by SSH, expression of MAGE-9 in RCC.…”

Section: -35mentioning

confidence: 99%

“…Cytotoxicity assay 51 Cr-labeled target cells were incubated in triplicate in 96-well plates with effector T cells at ratios of (T:E) 1:3-100. Cells were incubated for 4 hr (T2 cells) and 8 hr (RCC lines) at 37°C.…”

Section: Ifn-c Elispot Assaymentioning

confidence: 99%

“…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.…”

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confidence: 99%

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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

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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,

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Section: Discussionmentioning

confidence: 99%

“…Yet, the therapeutic efficacy remains below expectation. [48][49][50][51] We previously observed, by SSH, expression of MAGE-9 in RCC.…”

Section: -35mentioning

confidence: 99%

Section: Ifn-c Elispot Assaymentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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

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“…In search for RCC-associated peptides able to induce CTLs, we have identified three CA9 antigen-derived peptides, CA9p219-227, p288-296, and p323-331, and showed their ability to induce HLA-A24-restricted, CA9-specific CTLs (11). MN/CA9 was initially isolated as a tumor-associated antigen from HeLa cells (12) and belongs to the family of carbonic anhydrases catalyzing the conversion of carbon dioxide and water to carbonic acid, which is involved in various aspects of normal physiologic processes.…”

mentioning

confidence: 99%

A Phase I Trial of Vaccination of CA9-Derived Peptides for HLA-A24-Positive Patients with Cytokine-Refractory Metastatic Renal Cell Carcinoma

Uemura

Fujimoto

Tanaka

et al. 2006

Clinical Cancer Research

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Purpose: A phase I peptide vaccination trial was done in patients with progressive cytokinerefractory metastatic renal cell carcinoma (RCC) to assess both the toxicity and capability to induce immune responses of three peptides (CA9p219-227, p288-296, and p323-331) derived from CA9, a tumor-associated antigen ubiquitously expressed in RCC. Experimental Design: Twenty-three patients positive for human leukocyte antigen (HLA)-A24 with histologically confirmed RCC were enrolled. Eligibility included progressive disease after standard cytokine therapy with interleukin-2 and/or IFN-a. Patients were vaccinated s.c. with the three peptides emulsified in incomplete Freund's adjuvant at 2-week intervals. Pre-and postvaccination blood samples were obtained for toxicity assessment and immunologic studies. Patients were monitored for clinical responses on a 3-monthly basis. Results: Vaccinations were well tolerated without any major adverse event. Most of the patients developed peptide-specific CTLs and/or immunoglobulin G reactive to the peptides after the 6th or 9th vaccination, followed by a gradual increase in both CTL frequency and levels of peptidereactive serum IgG. Three patients with multiple lung metastases showed partial responses with disappearance and shrinking of metastatic lesions. Additionally, stable disease for >6 months was observed in six patients (median duration, 12.2 months). Moreover, the median survival time of all patients who were progressive at trial enrollment after failing immunotherapy was 21.0 months (5-35 months). Conclusions:These results suggest that vaccination of these peptides is safe and recommended for further trials for HLA-A24-positive metastatic RCC patients.

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Maintenance of WT1 expression in tumor cells is associated with a good prognosis in malignant glioma patients treated with WT1 peptide vaccine immunotherapy

Yokota

Kagawa

Takano

et al. 2021

Cancer Immunol Immunother

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Induction of antigen specific cellular immunity by vaccination with peptides from MN/CA IX in renal cell carcinoma

Cited by 13 publications

References 0 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

A Phase I Trial of Vaccination of CA9-Derived Peptides for HLA-A24-Positive Patients with Cytokine-Refractory Metastatic Renal Cell Carcinoma

Maintenance of WT1 expression in tumor cells is associated with a good prognosis in malignant glioma patients treated with WT1 peptide vaccine immunotherapy

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