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T J Eberlein

Publications and source records attributed to T J Eberlein.

At least 37 records · Page 2Linked to original sources
PubMed1997

Simultaneous production of T helper-1-like cytokines and cytolytic activity by tumor-specific T cells in ovarian and breast cancer.

Cytotoxic T-cell (CTL) cultures were generated from five ovarian cancer patients (OvCTL) and from three breast cancer patients (BrCTL). All CTL lines were T-cell receptor (TcR) alphabeta+ and predominantly CD8+ (73 +/- 13%). These CTL lines preferentially recognized autologous tumor cells in an HLA class I-restricted, and in part HLA-A2-restricted, manner. In addition, the CTL lines recognized allogeneic HLA-A2+ ovarian and breast tumor cells. Specific recognition was determined by T-cell-mediated cytotoxicity as well as cytokine release. Coculture of irradiated autologous tumor cells with OvCTL induced secretion of IFN-gamma, GM-CSF and TNF-alpha, but not IL-4, indicating a T helper-1-type response. Similar results were obtained when OvCTL and BrCTL were stimulated with histologically matched HLA-A2+ tumor cells. Also, BrCTL stimulated with HLA-A2+ but not HLA-A2- ovarian tumor cells produced significant levels of GM-CSF and TNF-alpha. Finally, the Her2/neu peptide p654-662, earlier identified as a tumor antigen in both ovarian and breast cancer, induced cytotoxicity as well as the specific release of IFN-gamma and TNF-alpha but not IL-4 by OvCTL and BrCTL. Thus, tumor-specific recognition by CTL was verified by cytotoxicity and cytokine release. The secretion of Th1-like cytokines as opposed to Th2-like cytokines suggest that therapeutically OvCTL and BrCTL could potentially enhance the endogenous immune response to tumor.

Antigens, Neoplasm↗
PubMed1997

The HER2/neu-derived peptide p654-662 is a tumor-associated antigen in human pancreatic cancer recognized by cytotoxic T lymphocytes.

The protooncogene HER2/neu encodes a 185-kDa transmembrane protein with extensive homology to the epidermal growth factor receptor. It is overexpressed in several human cancers of epithelial origin, such as pancreatic cancer. Previously, we demonstrated that cytotoxic T lymphocytes (CTL) derived from breast, ovarian, and non-small cell lung cancer recognized a peptide derived from HER2/neu. To evaluate whether this HLA-A2-binding peptide is a tumor-associated antigen (TAA) in pancreatic cancer, the ability of HER2/neu-reactive CTL to lyse human pancreatic carcinoma cells was tested. CTL were generated from tumor-associated T lymphocytes from HLA-A2+ HER2/neu+ breast and ovarian cancer patients. All CTL recognized autologous and allogeneic HER2/ neu+ tumor cells in an HLA-A2-restricted fashion. Furthermore, all CTL recognized p654-662 (GP2) derived from HER2/neu. These CTL also recognized HER2/neu+ pancreatic cancer cells in an HLA-A2-restricted fashion. HER2/neu+ HLA-A2- pancreatic cancer were not or only poorly lysed. Repeated stimulation of HLA-A2+ PBL from pancreatic cancer patients using the HER2/neu-derived peptide resulted in specific recognition of this peptide and, more importantly, HER2/neu+ pancreatic tumors in an HLA-A2-restricted fashion. Autologous HLA-A2+ fibroblasts or HLA-A2+ malignant melanoma cells were not recognized. HLA-A2- peptide-stimulated T lymphocytes showed no significant cytotoxicity. These results demonstrate that this HER2/neu-derived peptide is a shared TAA among several adenocarcinomas including pancreatic carcinoma, suggesting a common mechanism of recognition of these human tumors by T lymphocytes. The identification of the HER2/neu-derived peptide GP2 as a TAA in pancreatic cancer provides an opportunity for the design of novel immunotherapy and vaccine strategies.

Adenocarcinoma↗
PubMed1997

Generation of peptide-specific cytotoxic T lymphocytes using allogeneic dendritic cells capable of lysing human pancreatic cancer cells.

BACKGROUND: Dendritic cells (DCs) are potent antigen presenting cells (APCs), able to efficiently induce primary T cell-mediated responses to foreign antigens. In earlier studies we were able to identify a histocompatibility antigen (HLA)-A 2-restricted nine amino acid peptide (GP2, peptide 654-662) from the transmembrane portion of the protooncogene HER2/neu as a tumor-associated antigen (TAA) in human pancreatic cancer. METHODS: Peripheral blood mononuclear cells (PBMCs) of HLA-A2+ and HLA-A2 healthy volunteers were isolated. PBMCs were grown with initial anti-CD3, low-dose interleukin-2 (IL-2), and peptide-pulsed DC stimulation. T-cell lines were analyzed in functional studies. RESULTS: After 4 weeks, T-cell cultures were more than 50% CD8+. All peptide-pulsed T cells significantly lysed APC pulsed with the immunizing antigen in an HLA-A2 restricted fashion. Furthermore, HLA-A2+,HER2/neu+ human pancreatic cancer cells were lysed significantly higher than HLA-A2 HER2/neu+ pancreatic cancer cells. Transfection of an HLA-A2 pancreatic cancer cell line with the HLA-A2 gene resulted in a significantly higher lysis of the transfected cell line compared to the wild type. In HLA-A2+ pancreatic cancer targets, specific lysis was HLA-A2 restricted. CONCLUSION: The ability to use DCs for presentation of either tumor or peptide antigen in an HLA-restricted fashion to stimulate T-cell proliferation, as well as cytotoxicity, demonstrates the potential of this technology for future development of a pancreatic cancer vaccine.

Amino Acid Sequence↗
PubMed1997

[Cytotoxic T-lymphocytes and the recognition of tumor antigens--an approach to "preventive tumor vaccination?"].

In spite of modifications of the intra- and postoperative therapeutic strategy as well as new adjuvant protocols, most malignant diseases have a poor prognosis. This demonstrates the need for new approaches in tumor therapy. One alternative is adoptive immunotherapy (AIT). AIT is based on the observation that cytotoxic T-lymphocytes (CTL) may be generated with the ability to lyse autologous tumor cells in vitro and in vivo. Aim of current research activities is to determine specific tumorantigens and the clinical applicability of cell-mediated immunotherapy. The immunobiology of the cell-mediated immune response to cancer with focus on major-histocompatibility complex class I and CD8+ T cells is reviewed. Recent advances in the identification of tumor-associated and tumor-specific antigens were summarized. Previously performed clinical studies were reviewed. We examined the implications that the discovery of these antigens might have on the development of new anticancer vaccines.

Animals↗
PubMed1996

A prospective study of conservative surgery alone in the treatment of selected patients with stage I breast cancer.

BACKGROUND: Randomized clinical trials have clearly demonstrated that the use of radiation therapy (RT) following breast-conserving surgery (CS) substantially reduces the risk of local recurrence. However, the low rate of local recurrence after CS and RT for patients without known risk factors, and the recent increase in the detection of smaller cancers due to mammographic screening have led to the speculation that a subgroup of patients who have a low risk of local recurrence without RT might be identified. In 1986, we initiated a one-arm, prospective clinical trial of CS alone for treatment of highly selected breast cancer patients without known risk factors for local recurrence. METHODS: The study had a sequential design with a planned accrual of 90 patients. Criteria for entry into the trial were: a unicentric, clinical TI infiltrating ductal, mucinous or tubular carcinoma without an extensive intraductal component or lymphatic vessel invasion; a wide excision with a pathologically-documented negative margin of at least 1 cm; and histologically negative axillary lymph nodes. No adjuvant RT or systemic therapy was administered. Seventy-six per cent of the lesions were detected by mammography alone. The median gross pathologic tumor size was 0.9 cm. The median patient age was 67 years. RESULTS: Eighty-seven patients were enrolled in the trial before it closed prematurely in 1992 because the predefined stopping boundary was crossed (i.e., the sixth local recurrence was observed). At that time, the average annual local recurrence rate was 4.2%. With a median follow-up of 56 months, there are now 14 patients (16%) with local recurrence as their site of first failure (average annual local recurrence rate: 3.6%). Four patients without local recurrence developed distant metastases. Three patients have died, one of metastatic breast cancer and two of unrelated causes. CONCLUSIONS: Even in a highly selected group of patients with early-stage breast cancer, there is a substantial risk of early local recurrence for those treated with wide excision alone.

Adenocarcinoma, Mucinous↗
PubMed1996

Vaccine therapy for cancer.

BACKGROUND: Tumor-specific cytotoxic T-lymphocytes (CTLs) can be isolated from the solid tumors, draining lymph nodes, metastatic effusions, and peripheral blood of cancer patients. Despite this evidence for a cell-mediated immune response to cancer, attempts at active specific immunotherapy using cancer vaccines have met with little success in clinical trials. METHODS: We have reviewed the immunobiology of the cell-mediated immune response to cancer by focusing on what is known about the major histocompatibility complex (MHC)-restricted interaction between tumor cells and CD8+ or CD4+ T-cells. In addition, we review the recent advances in the identification of tumor-associated antigens (TAAs) that are recognized by tumor-specific CTLs in melanoma and other cancers. In discussing these antigens, we highlight the recent identification of several MHC-restricted antigenic peptides that are recognized by CTLs from patients with melanoma and those with ovarian and breast cancer. We examine the implications that the discovery of these TAAs and peptides will have on the development of new anticancer vaccines. We review the most recent vaccine trials in melanoma and other cancers and focus on current concepts aimed at improving the therapeutic efficacy of future vaccines, including genetically engineered tumor cell vaccines. CONCLUSIONS: With the recent identification of several TAAs and antigenic peptide epitopes in melanoma and other cancers, immunotherapy researchers are now focusing on new strategies for the development of anticancer vaccines. As the repertoire of known TAAs increases and our understanding of the immunobiology of cell-mediated immunity to cancer improves, immunotherapists remain cautiously optimistic in their quest for effective cancer vaccines.

Antigens, Neoplasm↗
PubMed1996

Improved in vivo efficacy of tumor-infiltrating lymphocytes after restimulation with irradiated tumor cells in vitro.

BACKGROUND: We investigated different culture conditions for tumor-infiltrating lymphocytes (TILs) with regard to proliferation, phenotypic changes, in vitro cytotoxicity, and in vivo therapeutic efficacy. METHODS: After enzymatic digestion of the murine fibrosarcoma, MCA-105, TIL cultures were initiated as pure lymphocyte (groups 1 and 2) or mixed lymphocyte/tumor suspensions (groups 3 and 4). Group I TILs were grown in culture medium containing 100 IU/ml recombinant interleukin-2 (rIL-2). Group 2 TILs were stimulated with solid-phase anti-CD3 monoclonal antibody (mAb) for 48 h and cultured in rIL-2 (100 IU/ml)-containing medium. Group 3, which consisted initially of a surplus of tumor cells, received the same treatment as group 2. Group 4 was also activated with anti-CD3 mAb and rIL-2 but was additionally restimulated weekly with irradiated tumor cells (TILs to tumor, 20:1). RESULTS: Groups 1 and 2 showed up to twofold higher increases in TIL numbers compared with groups 3 and 4 by the end of culture week 5. Although the original lymphocyte/tumor cell suspension consisted of 12.0 +/- 3.8% CD4+ T cells and 5.3 +/- 3.3% CD8+ T cells, all four TIL cultures showed approximately 80% CD8+ TILs and no CD4+ TILs by the end of culture week 4. In vitro cytotoxicity did not correlate with in vivo efficacy of the examined TIL cultures. By using the MCA-105 pulmonary metastases model in C57BL/6 mice, only suboptimal doses of TILs (2 x 10(6)) from group 4, which had been restimulated weekly with irradiated tumor, showed significant tumor eradication compared with all other treatment groups (p < 0.01). CONCLUSIONS: We conclude that in vitro tumor restimulation of TILs improves in vivo efficacy, most likely through the education of tumor-reactive T cells.

Animals↗
PubMed1995

Tumor-specific and HLA-A2-restricted cytolysis by tumor-associated lymphocytes in human metastatic breast cancer.

A tumor-specific cytotoxic T lymphocyte (CTL) immune response has been well documented in melanoma, renal cell carcinoma, and ovarian cancer. Conflicting evidence exists regarding the existence of tumor-specific CTL populations in breast cancer. Tumor cells and tumor-associated lymphocytes (TAL) were isolated from the pleural effusions of six consecutive patients with metastatic breast cancer. After solid-phase anti-CD3 stimulation, TAL cultures were expanded with weekly autologous tumor stimulation and low-dose IL-2 for 3 wk. T cell populations were characterized using flow cytometric analysis and ranged from 49 to 91% CD8+, > 98% CD3+, and < 3% CD16+. Functionally, tumor-stimulated TAL showed tumor-specific recognition of autologous tumor cells (241 +/- 142 LU20/10(7)) and no detectable lysis of autologous fibroblasts, Daudi or K562. Cytotoxicity of TAL against HLA-A2+ allogeneic targets was significantly higher when compared with HLA-A2- tumor cell lines (127 +/- 76 vs 6 +/- 18 LU, p = 0.0001). This cytotoxicity against autologous and allogeneic tumor cells was blocked by anti-HLA-A2 mAb and cold HLA-A2+ targets in cold-target inhibition assays. TAL from all HLA-A2+ patients recognized GP2, a known, HER2/neu-derived tumor-associated peptide Ag that is HLA-A2 restricted. We have shown that TAL obtained from metastatic effusions of breast cancer patients contain lymphocytes that can recognize and lyse autologous and allogeneic tumor cells in a tumor-specific, HLA-A2-restricted fashion. In addition, tumor-specific TAL derived from breast cancer patients can selectively lyse HLA-A2+ pancreatic and ovarian tumor cell targets, suggesting a common HLA-A2-restricted tumor-associated Ag between these distinct epithelial cancers. Further elucidation of the cell-mediated immune response to breast cancer and the identification of shared TAA could result in the development of broadly applicable vaccine therapies for many cancers.

Adenocarcinoma↗
PubMed1995

T lymphocytes that infiltrate tumors and atherosclerotic plaques produce heparin-binding epidermal growth factor-like growth factor and basic fibroblast growth factor: a potential pathologic role.

Despite significant infiltration into tumors and atherosclerotic plaques, the role of T lymphocytes in these pathological conditions is still unclear. We have demonstrated that tumor-infiltrating lymphocytes (TILs) and plaque-infiltrating lymphocytes (PILs) produce heparin-binding epidermal growth factor-like growth factor (HB-EGF) and basic fibroblast growth factor (bFGF) in vitro under nonspecific conditions and in vivo in tumors by immunohistochemical staining. HB-EGF and bFGF derived from TILs and PILs directly stimulated tumor cells and vascular smooth muscle cells (SMCs) in vitro, respectively, while bFGF displayed angiogenic properties. Therefore, T cells may play a critical role in the SMC hyperplasia of atherosclerosis and support tumor progression by direct stimulation and angiogenesis.

3T3 Cells↗
PubMed1995

Breast and ovarian cancer-specific cytotoxic T lymphocytes recognize the same HER2/neu-derived peptide.

The identification of antigenic peptides presented on the tumor cell surface by HLA class I molecules and recognized by tumor-specific cytotoxic T lymphocytes may lead to a peptide vaccine capable of inducing protective cellular immunity. We demonstrate that both HLA-A2-restricted breast and ovarian tumor-specific cytotoxic T lymphocytes recognize shared antigenic peptides. At least one of these peptides is derived from the oncogene product of HER2/neu, which is overexpressed in 30-40% of all breast and ovarian cancers. T cells sensitized against this nine-amino acid sequence demonstrate significant recognition of HLA-A2+, HER2/neu+ tumors. Since 50% of the tumor-cell population is HLA-A2+ and many different tumors express HER2/neu, this peptide may be widely recognized and have many clinical applications.

Antigens, Neoplasm↗
PubMed1995

Shared T cell epitopes in epithelial tumors.

We have previously shown the importance of human leukocyte antigen (HLA)-A2 and the proto-oncogene HER2/neu in the T cell recognition of ovarian cancer. Since these proteins are ubiquitously expressed in epithelial-derived tumors, we have acid-eluted HLA-bound peptides from ovarian cancers, fractionated the peptides, and reconstituted T cell epitopes on the HLA-A2+ T2 cell line to determine if common tumor-associated antigens exist among HLA-A2+, HER2/neu+ epithelial cancers. We demonstrate that tumor-specific cytotoxic T lymphocytes (CTL) generated from tumor-infiltrating lymphocytes isolated from three ovarian, two breast, and two non-small-cell lung cancers recognize at least three of the same peptide fractions from multiple elutions. One of these peptide fractions coelutes with a HER2/neu-derived peptide which has been shown recently to be recognized by these same CTL. These findings demonstrate that a common peptide-based tumor vaccine is theoretically possible for many different epithelial-derived cancers.

Antigens, Neoplasm↗
PubMed1995

Anti-tumor effects and tumor immunogenicity following IL2 or IL4 cytokine gene transfection of three mouse mammary tumors.

BACKGROUND: The anti-tumor effects of three mouse mammary tumors transfected to express interleukin (IL) 2 or 4 were evaluated. METHODS: Three immunologically different tumors were used: DA3, EMT6, and 410. All three cell lines were successfully transfected using high efficiency viral vectors. Wild-type or transfected tumor cells were injected subcutaneously into Balb/c mice and animals were observed for tumor growth. RESULTS: Overall, there was a significant decrease in the incidence and in the size of palpable transfected tumor compared with control tumors. Animals were immunized with wild-type or transfected cells and challenged with wild-type tumor. In these experiments, animals immunized with transfected tumor cells had a significantly lower incidence of tumor and significantly smaller tumors than controls. Similar experiments were performed by immunization with irradiated cells (wild type and transfected), and significant immune protection was induced. CONCLUSIONS: Each cell line responded differently following gene transfection, with the greatest anti-tumor effects seen in the EMT6 tumor cells transfected with IL2 or IL4.

Animals↗
PubMed1995

The role of CD4+ tumor-infiltrating lymphocytes in human solid tumors.

Many, if not all, solid tumors are characterized by a T cell infiltrate, usually consisting of CD4+ and CD8+ T cells. Characterization of both subsets of tumor-infiltrating lymphocytes (TIL) have shown that each population can be divided into tumor-specific and tumor-nonspecific T cells. A small proportion of tumor-specific CD4+ TIL can directly lyse tumor cells in an HLA class I- or II-restricted fashion. The majority of tumor-specific CD4+ TIL, however, recognize tumor antigens presented on HLA class II molecules by antigen-presenting cells (APC). At the same time, APC in the tumor environment express elevated levels of heat shock antigen (Hsp) 70 (and perhaps other antigens) that can be specifically recognized by tumor-nonspecific CD4+ TIL when presented by HLA class II. Functionally, CD4+ T cells can be distinguished into Th0 (production of IL-2, IL-4, and IFN-gamma), Th1 (IL-2 and IFN-gamma), and Th2 (IL-4). In addition, stressed CD4+ TIL have the ability to produce the growth factors heparin binding epidermal growth factor and basic fibroblast growth factor that support tumor growth. Since the efficacy of an antitumor immune response is codetermined by the net effect of stimulatory and inhibitory cytokines, a detailed understanding of the developmental pathways of CD4+ TIL subsets and their interactions is critical for the design of clinical protocols.

CD4-Positive T-Lymphocytes↗
PubMed1995

Immunoregulatory effects of CD4+ T helper subsets in human melanoma.

BACKGROUND: The elucidation of CD4+ T helper (Th) cell traits is important for the understanding of immunoregulatory mechanisms in patients with cancer, in particular the Th-cell effect on cytotoxic CD8+ tumor-specific lymphocytes (CTL). METHODS: Sixty-six T-cell receptor alpha beta+/CD4+ clones were generated from tumor-infiltrating lymphocytes of five patients with melanoma and classified into subsets by cytokine production. Transwell experiments were performed to test how the soluble factors of each Th-clone subset affected the cytotoxicity of the tumor-specific CTL against autologous tumor. RESULTS: Th0 clones enhanced cytotoxicity of the CD8+ CTL compared with control CTL cultured in cytokine-free medium. Th1-clone supernatant also enhanced cytotoxicity by CD8+ CTL. In contrast, Th2 clones decreased killing compared with control CTL. Replacement of the Th clones by exogenous interleukin (IL)-2 in concentrations similar to that produced by Th0 and Th1 clones enhanced cytotoxicity. However, suppression of cytotoxicity was observed when similar concentrations of IL-4 were added instead. The helper effect of Th0-soluble factors could be inhibited by anti-IL-2 antibody, whereas anti-IL-4 antibody did not show a significant enhancement. CONCLUSIONS: The majority of the CD4+ tumor-infiltrating lymphocytes (Th0) in patients with melanoma enhance the CTL response to autologous tumor by their soluble factors, whereas Th2 cells suppress the CTL response.

Antigens, CD↗
PubMed1995

Recruitment of host CD8+ T cells by tumor-infiltrating lymphocytes and recombinant interleukin-2 during adoptive immunotherapy of cancer.

BACKGROUND: Previously we demonstrated that optimal doses of tumor-infiltrating lymphocytes (TIL) concomitant with recombinant interleukin-2 (rIL-2) effectively mediated complete tumor regression of murine 3-day pulmonary metastases. METHODS: In the present study we have investigated the contribution of the host immune response to the effectiveness of adoptive immunotherapy with TIL in combination with low-dose rIL-2. All experiments were performed in a murine pulmonary metastases model induced by intravenous injection of methylcholanthrene-induced sarcoma (MCA-105) cells into C57BL/6 mice. As a novel approach we used monoclonal antibody specific for CD4+ or CD8+ T cells to deplete the host of its T-cell subpopulations. RESULTS: Depletion of host CD8+ T cells 24 hours after tumor injection and 48 hours before TIL+rIL-2 treatment abrogated all antitumor activity of this type of immunotherapy and resulted in significant metastatic pulmonary disease (p < 0.001). In contrast, depletion of host CD4+ T cells did not alter the efficacy of TIL+rIL-2 treatment in tumor eradication. The loss of tumoricidal activity of TIL+rIL-2 treatment in a CD8+ T cell-depleted host could be overcome by adding back normal uneducated splenocytes 2 hours after TIL therapy (p < 0.001). In contrast, adding back CD8- CD4+ splenocytes to a CD8+ T cell-depleted host 2 hours after TIL+rIL-2 treatment resulted in significant pulmonary disease comparable to untreated animals. CONCLUSIONS: We conclude that the recruitment of host CD8+ T cells by adoptively transferred TIL+rIL-2 appears to be important for effective tumor eradication in this type of immunotherapy.

Animals↗
PubMed1995

Antitumor activity of three mouse mammary cancer cell lines after interferon-gamma gene transfection.

BACKGROUND: The antitumor effects of three mouse mammary tumors transfected to express interferon-gamma were evaluated. METHODS: Three immunologically different tumors were used: DA3, EMT6, and 410. All three cell lines were successfully transfected with highly efficient viral vectors. Wild type or transfected tumor cells were injected subcutaneously into Balb/c mice. Animals were observed for tumor growth and the induction of immunologic memory. RESULTS: A significant decrease occurred in the size of all transfected tumors, EMT6 1.9 cm2, DA3 1.7, and 410 1.8 compared with nontransfected control tumors with a mean size of 4 cm2 on day 30. To further test the development of immunity, animals were injected with either nontransfected or transfected tumors and challenged with nontransfected tumor. Animals immunized with transfected tumor cells had significantly smaller tumors, EMT6 2.5 cm2, DA3 3.1, and 410 2.4 compared with controls with a mean size of 4 cm2. No specific splenocyte cytotoxicity was shown. Expression of major histocompatibility complex class I antigens was enhanced in the 410 and DA3 tumor lines. CONCLUSIONS: Significant antitumor effects were observed after interferon-gamma gene transfection of three mouse mammary cancer cell lines. Up-regulation of major histocompatibility complex class I antigen expression is a partial explanation of these findings. These results provide preliminary studies for gene therapy of human breast cancer.

Animals↗
PubMed1995

In vitro stimulation of ovarian tumour-associated lymphocytes with a peptide derived from HER2/neu induces cytotoxicity against autologous tumour.

The proto-oncogene HER2/neu encodes for a 185 kDa transmembrane protein with extensive homology to the epidermal growth factor (EGF) receptor. We have previously shown a correlation between HER2/neu expression and the level of in vitro cytotoxicity of tumour-associated lymphocytes (TAL) versus autologous tumour. In addition, we have recently demonstrated that tumour-associated cytotoxic T-lymphocytes (CTL) from ovarian and breast cancer patients can recognize a HER2/neu derived peptide epitope when presented in the context of HLA-A2. Since repeated tumour stimulation of CTL enhances both proliferation and cytotoxicity against autologous tumour, we hypothesized that repeated peptide antigen stimulation would have a similar effect. To be therapeutically useful, the peptide antigen must meet the following conditions: (1) the peptide must be immunogenic and cause a proliferation of CTL to adequate therapeutic numbers, and (2) the peptide-specific CTL which are generated must be cytotoxic against autologous tumour. To test our hypothesis, T-lymphocytes isolated from the ascites of four consecutive HER2/neu+ ovarian cancer patients were initially stimulated with solid phase anti-CD3 antibody and divided into three groups: (1) treatment with recombinant interleukin-2 (IL-2) alone, (2) IL-2 plus weekly stimulation with irradiated autologous tumour cells, and (3) IL-2 plus weekly stimulation with a HER2/neu derived peptide. Peptide-stimulated and tumour-stimulated CTL showed similar increases in proliferation with both groups consistently reaching therapeutic numbers. Peptide-stimulated CTL demonstrated significantly enhanced cytotoxicity against autologous tumour in 4-h chromium release assays as compared to the IL-2 alone group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗