Recombinant Interleukin-2-Expanded Tumor Infiltrating Lymphocytes from Human Renal Cell Cancer Do Not Exhibit Autologous Tumor Cell-Specific Cytotoxicity

Nishimura, Takuya; Terashima, Y.; Hattori, T; Satoh, Mitsuhiro; Kondo, Yutaro; Kimura, Go; Yoshida, Kosaku; Akimoto, Masumi

doi:10.1159/000282260

Cited by 6 publications

(2 citation statements)

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“…Several laboratories have previously developed T cell lines from RCC TIL using various concentrations of rIL-2 [5,[14][15][16][17][18][19][20]. Most of these T cell lines exhibited a wide range of cytotoxicity against autologous and allogeneic renal tumour cells and NK-sensitive targets.…”

Section: Discussionmentioning

confidence: 99%

Characterization of fresh (uncultured) tumour-infiltrating lymphocytes (TIL) and TIL-derived T cell lines from patients with renal cell carcinoma

Mitropoulos

Rodríguez‐Villanueva

Platsoucas

1994

Clinical and Experimental Immunology

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SUMMARYFresh (uncultured) TIL from 12 untreated patients with primary renal cell carcinoma were prepared from tumour specimens by enzymatic digestion, and were characterized by immunotluorescence using MoAbs recognizing leucocyte differentiation antigens or particular Va or V/? segments of the T cell receptor (TCR). These fresh TIL comprised CD3+ (20-84%); CD4+ (3-15%); CD8+ (13-35%); a/3TCR^ (20 50%); 7<5TCR+ (3-17%); CD16+ (1-18%) and CD56( 3-10%) cells. Significant proportions of VQ2"', V^5.1+ and V^6+ cells were found in TIL of certain patients with renal cell carcinoma, suggesting that they comprised oligoclonal T cells. T cell lines were developed in low concentrations of rIL-2 (200 U/ml) from TIL from II patients wiih renal cell carcinoma, and were characterized by immunofluorescence and cell-mediated cytotoxicity. These T cell lines consisted primarily of CD3^ (51-94%); CD4+ (1 80%); CD8+ (0-84%); Q/3TCR+ (65-87%); 7^TCR+ (0-25%); CDI6+ (0-16%) and CD56+ (2-57%) cells. These Tcell lines exhibited non-specific cytotoxicity against autologous and aliogeneic renal tumour cells, with the exception of one T cell line that exhibited preferential cytotoxicity against autoiogous renal tumour cells. These results suggest that fresh TIL from patients with renal cell carcinoma contain significant proportions of oligoclonal T cells that may have accumulated at the tumour site as a result ofa clonal expansion.

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Section: Discussionmentioning

confidence: 99%

Characterization of fresh (uncultured) tumour-infiltrating lymphocytes (TIL) and TIL-derived T cell lines from patients with renal cell carcinoma

Mitropoulos

Rodríguez‐Villanueva

Platsoucas

1994

Clinical and Experimental Immunology

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“…Although clinical responses to IL-2 had been reported in both cancers [14,15], the coadministration of TIL with IL-2 resulted more efficient only in melanoma patients [16]. This was attributed to the paucity of tumor-specific CD8 T cell among IL-2-expanded TIL from renal cell carcinomas [17,18], in sharp contrast with the frequent presence of such cells among melanoma TIL [2]. Therefore, ACT using TIL were essentially pursued in melanomas.…”

Section: Introductionmentioning

confidence: 99%

Adoptive transfer with high-affinity TCR to treat human solid tumors: how to improve the feasibility?

2012

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The adoptive transfer of tumor antigen-specific T cells recently achieved clinical efficacy for a fraction of melanoma patients refractory to other therapies. Unfortunately, the application of this strategy to the remaining melanoma and most other cancer patients is hampered by the difficulty to generate high-affinity tumor-reactive T cells. Two strategies are currently developed to extend the feasibility of this therapeutic approach: clinical grade tool production for MHC-peptide multimer-driven sorting of antigen-specific T cells from the endogenous peripheral T cell repertoire and de novo engineering of the missing repertoire by genetic transfer of cloned specific T cell receptor (TCR) into T cells. The expected multiplication of adoptive transfer treatments, by these strategies, and their careful evaluation should enable the cure of a number of otherwise compromised cancer patients and to gain insight into the characteristics of transferred T cells best fitted to eradicate tumor cells, in terms of antigen specificities, phenotype, and functions. In particular, identification of tumor-rejection antigens by this approach would improve the design and efficacy of all immunotherapeutic approaches.

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Tumor specific cytolysis by tumor infiltrating lymphocytes in breast cancer

Baxevanis¹,

Dedoussis²,

Papadopoulos³

et al. 1994

Cancer

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Background. In vitro studies have demonstrated that exposure of tumor infiltrating lymphocytes (TIL) to human recombinant interleukin‐2 (rIL‐2) will generate activated T‐lymphocytes with major histocompatibility complex (MHC)‐restricted and non‐MHC‐restricted cytotoxicity toward a panel of tumor target cells. In melanoma and ovarian carcinoma, TII. display MHC‐restricted and autologous tumor‐specific cytotoxicity. Such tumor‐reactive cytotoxic T‐lymphocytes (CTL) represent important material for understanding cellular immunity in cancer and developing specific immunotherapeutic approaches in melanoma and ovarian cancer. In breast cancer, some TIL have been demonstrated to secrete cytokines upon interaction with autologous tumor cells, indicating that autologous tumor‐reactive lymphocytes may also exist among TIL in breast cancer. Therefore, the authors conducted a study to investigate the cytotoxic profile of rIL‐2‐activated lymphocytes in breast cancer. Methods. Lymphocytes were isolated from primary solid tumors (TIL) of breast carcinomas (10 patients) and from peritoneal effusions (effusion‐associated mononuclear cells [EAMNC]) from 2 patients with newly diagnosed metastatic breast carcinoma. Tumor infiltrating lymphocytes or EAMNC were cultured with rIL‐2 in long term cultures whereby their expansion index, phenotype, and cytotoxic potential were studied. Results. Both TIL and EAMNC proliferated by greater than 300‐fold (370‐3650; mean, 1656) after 23‐82 days in cultures containing mixtures of TIL or EAMNC, autologous tumor cells, and rIL‐2. By fluorescence analysis, freshly isolated TIL and EAMNC were found to consist of 77.5 plus or minus 10.7% CD3+ T‐cells, 33.2 plus or minus 8.9% CD4+, and 47.2 plus or minus 16.8% CD8+ cells. Their CD4 to CD8 ratio was 0.70. After expansion of lymphocytes with rIL‐2 in the majority of patients (9 of 12), CD3+CD8+ T‐lymphocytes were present in greater numbers than CD3+CD4+ T‐lymphocytes. Recombinant interleukin‐2‐activated CD3+CD8+ cells exhibited preferential cytolytic activity against autologous tumor cells. The cytolytic activity of CD3+CD8+ cells was inhibited either by anti‐T‐cell receptor (TCR)‐α/‐β and anti‐CD3 monoclonal antibodies (MoAb) or after pretreatment of tumor target cells with MoAb against the class I MHC antigens. Recombinant interleukin‐2‐activated CD3+CD4+ cells demonstrated potent cytolytic activity against both autologous and allogeneic tumor cells. CD3+CD8+ T‐cell clones isolated from representative TIL exhibited preferential autologous tumor‐specific cytotoxicity whereas the cytolytic activity of CD3+CD4+ T‐cell clones was mostly (12 of 14 clones) nonrestricted to the autologous tumor. Conclusions. To the authors' knowledge, this is the first report to demonstrate that TIL from primary tumors of breast carcinomas and EAMNC from metastatic disease can be propagated in large numbers in vitro with rIL‐2 while retaining autologous tumor specific and MHC‐restricted CTL activity. These findings may be of importance to ongoing clinical trials usi...

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Recombinant Interleukin-2-Expanded Tumor Infiltrating Lymphocytes from Human Renal Cell Cancer Do Not Exhibit Autologous Tumor Cell-Specific Cytotoxicity

Cited by 6 publications

References 1 publication

Characterization of fresh (uncultured) tumour-infiltrating lymphocytes (TIL) and TIL-derived T cell lines from patients with renal cell carcinoma

Characterization of fresh (uncultured) tumour-infiltrating lymphocytes (TIL) and TIL-derived T cell lines from patients with renal cell carcinoma

Adoptive transfer with high-affinity TCR to treat human solid tumors: how to improve the feasibility?

Tumor specific cytolysis by tumor infiltrating lymphocytes in breast cancer

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