The In Vitro Generation of Effector Lymphocytes and Their Employment in Tumor Immunotherapy

Kedar, Eli; Weiss, David

doi:10.1016/s0065-230x(08)60190-6

Cited by 46 publications

(14 citation statements)

References 693 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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“…Various investigators have attempted to obtain cytotoxic lymphocytes directed against syngeneic tumors by direct in vitro stimulation of responding cells with the tumor (MLTC sensitization) [14]. The more notable successes have been achieved with tumor lines that had been chemically or virally induced and repeatedly passaged; other lines failed to elicit a cytotoxic response and are hence defined as nonimmunogenic [14,29].…”

Section: Discussionmentioning

confidence: 99%

“…The more notable successes have been achieved with tumor lines that had been chemically or virally induced and repeatedly passaged; other lines failed to elicit a cytotoxic response and are hence defined as nonimmunogenic [14,29].…”

Section: Discussionmentioning

confidence: 99%

“…Most studies aimed at obtaining cytotoxic lymphocytes against syngeneic tumors in experimental systems have involved virally or chemically induced, highly immunogenic tumor cell lines, many of which have been repeatedly passaged in vitro or in vivo for long periods [14]. In the course of passage, tumor lines may undergo phenotypic and antigenic changes [1,6,10,14,17,18,28] which are not necessarily associated with the neoplastic state of the original tumor cell.…”

Section: Introductionmentioning

confidence: 99%

“…In the course of passage, tumor lines may undergo phenotypic and antigenic changes [1,6,10,14,17,18,28] which are not necessarily associated with the neoplastic state of the original tumor cell. In an attempt to minimize the gross artifacts that might be found with highly immunogenic or long-passaged tumor lines, and to establish a model system more relevant to 'spontaneously' arising neoplasms, we decided to explore the cytotoxic response against a nonimmunogenic X-irradiation-induced lymphoma which has been maintained in culture for only a limited period of time.…”

Section: Introductionmentioning

confidence: 99%

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In vitro elicitation of cytotoxic response against a nonimmunogenic murine tumor by allosensitization

Leshem

Gotsman

Kedar

1984

Cancer Immunol Immunother

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The murine lymphoma (thymoma) PIR-2 of C57BL/6 origin, primarily induced in our laboratory by fractionated X-ray irradiation, has been shown to be nonimmunogenic by its failure to immunize syngeneic mice in vivo or to evoke a cytotoxic response in primary mixed lymphocyte-tumor cell cultures (MLTC) in vitro. We were able, however, to demonstrate the existence of anti-PIR-2 cytotoxic cells among allogeneic-primed C57BL/6 responding lymphocytes using the technique of limiting dilution cultures (LDC). The frequency of anti-PIR-2 cytotoxic cells among C57BL/6 lymphocytes sensitized against BALB/c splenocytes in mixed leukocyte culture (MLC) was 1/20 to 1/40, and the cytotoxic activity of positive LDC wells against PIR-2 reached 60% as determined by a 4-h 51Cr-release assay. The frequency of anti-PIR-2 cytotoxic cells could be increased two- to 10-fold (up to 1/4) by removing nylon-wool-adherent cells from the primed cell population and/or by enriching the primed lymphoblast population on a Percoll density gradient. Anti-PIR-2 cytotoxic cells were found to be Thy1+; Lyt1-2+ cells. Clones isolated from the LDC wells manifested strong cytotoxic activity toward PIR-2 cells and the stimulating BALB/c splenocytes but not against other H-2b tumor lines or C57BL/6 splenocytes. We suggest that the procedure of allostimulation in MLC-LDC is an effective in vitro means of generating highly reactive cytotoxic cells against poorly immunogenic neoplasms.

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A Cytotoxic T-Lymphocyte Clone Derived From Mice With Progressively Growing Tumors

Hoover

Inge²,

Frank³

et al. 1991

Arch Surg

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Tumor-specific T-cell clones were derived from spleen cells of mice bearing a syngeneic PHS-5 tumor (a P815 mastocytoma mutant). Cells were expanded in vitro and characterized and assayed for activity against the relevant tumor in vivo. Clone cells were CD4-, CD8+ T lymphocytes, as determined by fluorescence activated cell sorting analysis and were specifically cytotoxic against P815 tumor cells in vitro, as shown in chromium 51 release assays. These cells require both antigen and interleukin 2 to proliferate; neither alone is sufficient, even with the addition of interleukin 1. In an experimental P815 liver metastasis model, the adoptive transfer of GD11 or GD11.17 clone cells and injection of recombinant interleukin 2 (7500 U intraperitoneally) 3 days after infusion of tumor cells reduced the number of tumor nodules, while the adoptive transfer of lymphokine-activated killer cells was ineffective.

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The In Vitro Generation of Effector Lymphocytes and Their Employment in Tumor Immunotherapy

Cited by 46 publications

References 693 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

In vitro elicitation of cytotoxic response against a nonimmunogenic murine tumor by allosensitization

A Cytotoxic T-Lymphocyte Clone Derived From Mice With Progressively Growing Tumors

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