Human tumour antigens defined by cytotoxicity and proliferative responses of cultured lymphoid cells

Vose, Brent M; Bonnard, Guy D.

doi:10.1038/296359a0

Cited by 70 publications

(50 citation statements)

References 11 publications

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“…Preliminary results reveal the presence of significant numbers of Leu 4 + Leu 2A + lymphoblasts, after 6-day MLTC microcultures. It is envisaged that these cells may have tumour-specific cytotoxic capabilities [14,20,21] -at present being evaluated -and that they may be expanded for use in adoptive immunotherapy of patients with colorectal carcinoma [8,24,25].…”

Section: Discussionmentioning

confidence: 99%

In vitro generation of tumour-specific lymphocyte reactivity to colonic carcinoma cells

Kuppner

Wilkinson

Casson

et al. 1987

Cancer Immunol Immunother

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Purified tumour cells and normal mucosa cells from fresh human colorectal cancer resection specimens, and T-cell-enriched autologous peripheral blood lymphocytes, were mixed in short-term (6 day) mixed lymphocyte-tumour cell (MLTC) microcultures. Lymphocyte stimulation was measured by 3H-thymidine uptake, and a stimulation index (SI = [lymphocytes vs tumour cells (cpm)-tumour cells (cpm)]/[lymphocytes (cpm)] greater than 3 was regarded as significant. Significant lymphocyte reactivity was found in 10/15 patients with colon carcinoma. However, 1 patient with autologous tumour reactivity, also showed significant stimulation against autologous normal mucosa cells, suggesting tumour-associated reactivity. Maximum stimulation occurred most frequently at a lymphocyte:tumour cell ratio of 2:1 and with nylon wool-passaged lymphocytes.

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Section: Discussionmentioning

confidence: 99%

In vitro generation of tumour-specific lymphocyte reactivity to colonic carcinoma cells

Kuppner

Wilkinson

Casson

et al. 1987

Cancer Immunol Immunother

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“…In all experiments IL-2 and ECSM served as positive controls. DISCUSSION The idea that the tumor environment contains lymphocytes that may exhibit antitumor activity was the basis for using lymphocytes expanded'in culture as' therapeutic agents (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Much work supports the'concept that an immune response is initiated against tumors via direct tumor celllymphocyte contact, followed by the secretion of factors mitogenic for lymphocytes from several immunocyte sources.…”

Section: Methodsmentioning

confidence: 64%

“…Further investigation showed that the observed proliferative stimulation by the fourth tumor line was due to secreted factor(s) as mitogenic activity was present in the serum-free tumor cell supernatant. Both immunologic analyses of this medium and proliferative assays in which TILs were stimulated with recombinant lymphokine standards suggest the presence of a yet uncharacterized T-cell mitogen.The idea that the tumor environment is intrinsically immunogenic and, therefore, contains lymphocytes with the potential to induce tumor regression has led to the use of tumor-infiltrating lymphocytes (TILs) in clinical trials (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). In this procedure lymphocytes are grown ex vivo directly from tumors in the presence of the lymphokine interleukin 2 (IL-2); patients are reinfused with their TILs after the latter have been expanded in culture for several weeks.…”

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confidence: 99%

Mitogenic stimulation of human tumor-infiltrating lymphocytes by secreted factor(s) from human tumor cell lines.

Packard

1990

Proc. Natl. Acad. Sci. U.S.A.

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Tumor-infiltrating lymphocytes (TILs) have shown in vivo antitumor efficacy in both animal and human studies. Functions thought necessary for antitumor activity include cytolysis, homing, and proliferation at tumor sites. TILs, which are T lymphocytes grown ex vivo directly from tumors, bear interleukin 2 (IL-2) receptors capable of transducing the IL-2 mitogenic signal. However, IL-2 is not normally synthesized by solid tumor cells. This study was aimed at exploring the possible presence of T-cell mitogens of tumor origin. To this end four TIL lines derived from four melanoma patients were studied for their ability to use the environments of cultured tumor cell lines as mitogenic sources. The presence of four irradiated cultured human tumor cell lines, three of which were derived from the same melanoma patients as the TILs, were found to stimulate proliferation of human TILs in the absence of IL-2. Further investigation showed that the observed proliferative stimulation by the fourth tumor line was due to secreted factor(s) as mitogenic activity was present in the serum-free tumor cell supernatant. Both immunologic analyses of this medium and proliferative assays in which TILs were stimulated with recombinant lymphokine standards suggest the presence of a yet uncharacterized T-cell mitogen.The idea that the tumor environment is intrinsically immunogenic and, therefore, contains lymphocytes with the potential to induce tumor regression has led to the use of tumor-infiltrating lymphocytes (TILs) in clinical trials (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). In this procedure lymphocytes are grown ex vivo directly from tumors in the presence of the lymphokine interleukin 2 (IL-2); patients are reinfused with their TILs after the latter have been expanded in culture for several weeks. Although 60% of metastatic melanoma patients who had not previously received any immunotherapy showed objective responses in the largest clinical TIL trial to date (15), the characteristics of the tumor environment that produces TILs in vivo remain unclear.Two classes of stimuli-one derived from cell-cell contact between tumor cells and immunocytes and the other from soluble factors-may influence T-cell homing and proliferation. IL-2 is a potent mitogen for T cells, the cell type of TILs used (Table 1); however, its biosynthesis appears to be confined to immunocytes (16). This fact is consistent with the current belief that immunologically competent cells such as lymphocytes and monocytes represent the major sources of secreted mitogenic stimulation for lymphocytes. In this study the subject of soluble factors secreted by tumor cell lines as sources of stimuli for lymphocyte proliferation was addressed.As a starting point for this work, the issue of whether a tumor cell line established from a melanoma tumor could stimulate the growth of TILs derived from melanoma masses was examined. After confirming the amplification potential of three melanoma cell lines, a nonmelanoma line was tested for the same bioactivity and found...

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“…As stated above in this paper, EAL cells from cancer patients contained viable tumor cells. Vose and Bonnard (1982) and Vankey and Klein (1982) reported in the induction of autologous tumor specific-cytotoxic lymphocytes by mixed culture of PBL with untreated autologous tumor cells. In such a mixed lymphocytes-tumor cell culture (MLTC) lytic potential to autologous tumor has been generated by many investigators (Vankey and Koyama et al 1989a).…”

Section: Resultsmentioning

confidence: 99%

Functional and phenotypic characteristics of effusion-associated lymphoid cells cultured in the presence of either recombinant interleukin 2 or T-cell growth factor from malignant pleural and peritoneal effusions in patients with advanced carcinoma.

Ebihara

Koyama

1990

Tohoku J. Exp. Med.

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Human tumour antigens defined by cytotoxicity and proliferative responses of cultured lymphoid cells

Cited by 70 publications

References 11 publications

In vitro generation of tumour-specific lymphocyte reactivity to colonic carcinoma cells

In vitro generation of tumour-specific lymphocyte reactivity to colonic carcinoma cells

Mitogenic stimulation of human tumor-infiltrating lymphocytes by secreted factor(s) from human tumor cell lines.

Functional and phenotypic characteristics of effusion-associated lymphoid cells cultured in the presence of either recombinant interleukin 2 or T-cell growth factor from malignant pleural and peritoneal effusions in patients with advanced carcinoma.

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