Interferon-?-induced increased sensitivity ofHER2/neu-overexpressing tumor cells to lymphokine-activated killer cell lysis: importance of ICAM-1 in binding and post-binding events

Fady, Catherine; Gardner, Agnes; Gera, Joseph; Lichtenstein, Alan

doi:10.1007/bf01518456

Cited by 12 publications

(9 citation statements)

References 24 publications

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“…Moreover, specific recognition of cdr2 in tumor cells was enhanced by pretreating them with IFN-␥ (Fig. 2C), a cytokine that increases MHC class I expression, antigen processing, and ICAM expression (24,25). Neither treated nor untreated A2.1 Ϫ HeLa cells were recognized, confirming that target recognition was A2.1-restricted.…”

Section: Cdr2 (290) Peptide Is Naturally Processed and Recognized In mentioning

confidence: 80%

A T cell receptor associated with naturally occurring human tumor immunity

Santomasso

Roberts

Thomas

et al. 2007

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

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The onconeural antigens appear to serve as tumor rejection antigens in the paraneoplastic neurologic disorders. Here, we used an unbiased peptide binding screen, followed by studies in HLA-A2.1 transgenic mice to identify naturally processed HLA-A2.1 restricted epitopes of the paraneoplastic cerebellar degeneration breast/ ovarian cancer antigen cdr2. These mice were used to clone high-avidity cdr2-specific CD8 ؉ T cells that recognize human tumor cells presenting endogenously loaded MHC class I-cdr2 peptide. T cells with this specificity were detected in the peripheral blood of two HLA-A2.1 ؉ paraneoplastic cerebellar degeneration patients. We cloned T cell receptor (TCR) ␣ and ␤ genes from cdr2-specific T cells; electroporation of RNA encoding this TCR turned nonreactive donor T cells into efficient killers of human cdr2-expressing tumor cells. Cloned cdr2-specific TCR genes provide a clinically relevant means for immunologic targeting of human gynecologic cancers.gene therapy ͉ gynecologic cancer ͉ paraneoplastic cerebellar degeneration A new strategy for treating cancer patients has emerged from efforts to stimulate CD8 ϩ cytotoxic T lymphocytes (CTL) through vaccination or adoptive T cell transfer (1-3). This effort has relied on a growing list of human tumor antigens recognized by CTL. However, few of these tumor antigens are associated with naturally robust immune responses and spontaneous tumor rejection, and their clinical utility is unclear. The paraneoplastic neurologic disorders (PNDs), perhaps the best-known examples of naturally occurring tumor immunity (4-7), offer a different approach to this problem. For example, patients with paraneoplastic cerebellar degeneration (PCD) develop an antigen-specific and clinically robust antitumor immune response directed against their breast and ovarian carcinomas (5,8). In one series, two-thirds of PCD patients (34 of 52) presented with neurologic symptoms before the diagnosis of cancer, 87% (45 of 52) had limited oncologic disease when diagnosed, and tumor could only be found by exploratory surgery in 4 of 52; by comparison, only 50-60% of unselected breast cancer patients and 25% of ovarian cancer patients present with limited-stage disease (9).Expression of the PCD antigen, cdr2, is believed to be largely restricted to cerebellar Purkinje neurons (10). The immune system is thought to initiate PCD when cdr2 is abnormally made in breast or ovarian tumors, triggering an antitumor immune response that can break immune tolerance in the brain. Interestingly, cdr2 is expressed by a large proportion of breast (25%) and ovarian (60%) tumors from individuals who do not develop neurological disease (11). Taken together with observations of immune responses made in other PNDs (5-7), cdr2 expression, and perhaps immune responses to it, may develop independently of autoimmune responses. These observations suggest the possibility that some gynecologic cancer patients might benefit from cdr2-directed immunotherapy. In addition, the unique expression of cdr2 in tumor cells (...

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Section: Cdr2 (290) Peptide Is Naturally Processed and Recognized In mentioning

confidence: 80%

A T cell receptor associated with naturally occurring human tumor immunity

Santomasso

Roberts

Thomas

et al. 2007

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

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“…1 B and D). However, attempts to obtain recognition by these CTL lines of A2.1-expressing tumors that naturally expressed high levels of Hu p53 were unsuccessful, even after pretreatment of target cells with both interferon y (IFN-y) and tumor necrosis factor a (TNF-a) (data not shown), a method that is known to augment specific cell lysis by increasing the numbers both of MHC-peptide complexes and of adhesion molecules expressed on the cell surface (53,54 (18)(19)(20)24). However, A2.1-restricted…”

Section: Resultsmentioning

confidence: 99%

Targeting p53 as a general tumor antigen.

Theobald

Biggs

Dittmer

et al. 1995

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

255

220

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A major barrier to the design of immunotherapeutics and vaccines for cancer is the idiosyncratic nature of many tumor antigens and the possibility that T cells may be tolerant of broadly distributed antigens. We have devised an experimental strategy that exploits species differences in protein sequences to circumvent tolerance of highaffinity T cells. HLA transgenic mice were used to obtain cytotoxic T lymphocytes specific for peptides from the human p53 tumor-suppressor molecule presented in association with HLA-A2

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“…Cellular adhesion molecules such as ICAM-1, ICAM-2, LFA-3 and MHC class I and II antigens have been proposed by some investigators as playing an auxiliary but critical role in the initial contact between immune effectors and target tumour cells, but the proposition is not universally accepted (De Fries and Golub, 1988;Robertson et al, 1990;Correale et al, 1992;Galandini et al, 1992;Triozzi et al, 1992;Fady et al, 1993;Foreman et al, 1993;Henkart, 1994;Katsanis et al, 1994). In agreement with the majority of these reports, our results indicate that the expression of ICAM-1, ICAM-2, LFA-3 and MHC class I and II molecules are not associated with the RA-induced susceptibility of SC-Mi cells to LAK lysis.…”

Section: Discussionmentioning

confidence: 99%

All-trans retinoic acid decreases susceptibility of a gastric cancer cell line to lymphokine-activated killer cytotoxicity

Chao¹,

Jiang²,

Shyu³

et al. 1997

Br J Cancer

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Summary All-trans retinoic acid (RA) was previously shown to regulate the growth of gastric cancer cells derived from the cell line SC-Mi. This study was designed to investigate the effect of RA on the sensitivity of SC-Mi cells to lymphokine-activated killer (LAK) activity. RA at the concentration range of 0.001-10 kM was shown to induce SC-Mi cells to exhibit resistance to LAK activity in a dose-dependent manner. A kinetics study indicated that a significantly increased resistance was detected after 2 days of co-culturing SC-Mi cells with RA and reached a maximum after 6 days of culture. Similar results were obtained from two other cancer cell lines: promyelocytic leukaemia HL-60 and hepatic cancer Hep 3B. A binding assay demonstrated that the binding efficacy between target SC-M1 cells and effector LAK cells was not altered by RA. Flow cytometric analyses revealed that RA exhibited no effect on the expression of cell surface molecules, including HLA class and class 11 antigens, intercellular adhesion molecule-1 and -2, and lymphocyte function antigen-3. Cell cycle analysis revealed that culture of SC-Mi cells with RA resulted in an increase in GJG, phase and a decrease in S phase, accompanied by a decrease in cyclin A and cyclin Bi mRNA as determined by Northern blot analysis. Additionally, RA was shown to enhance the expression of retinoic acid receptor a (RARa) in SC-Mi cells, and to have no effect on the expression of RARfi or RARy. Taken together, these results indicate that RA can significantly increase gastric cancer cells SC-Mi to resist LAK cytotoxicity by means of a cytostatic effect through a mechanism relating to cell cycle regulation. The prevailing ideas, such as a decrease in effector to target cell binding, a reduced MHC class antigen expression or an altered RARP expression, are not involved.

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Interferon-?-induced increased sensitivity ofHER2/neu-overexpressing tumor cells to lymphokine-activated killer cell lysis: importance of ICAM-1 in binding and post-binding events

Cited by 12 publications

References 24 publications

A T cell receptor associated with naturally occurring human tumor immunity

A T cell receptor associated with naturally occurring human tumor immunity

Targeting p53 as a general tumor antigen.

All-trans retinoic acid decreases susceptibility of a gastric cancer cell line to lymphokine-activated killer cytotoxicity

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