[18] Poly-l-lysine-induced immobilization of tumor cells to plastic for the study of cellular metabolic responses to attack by cytotoxic T lymphocytes

1983 ◽  
pp. 260-270 ◽  
Author(s):  
Carmen A. Sepulveda ◽  
Seymour I. Schlager
Keyword(s):  
T Lymphocytes ◽  
Tumor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Metabolic Responses

scholarly journals Tumor Eradication by Wild-type p53-specific Cytotoxic T Lymphocytes

1997 ◽  
Vol 186 (5) ◽  
pp. 695-704 ◽  
Author(s):  
Michel P.M. Vierboom ◽  
Hans W. Nijman ◽  
Rienk Offringa ◽  
Ellen I.H. van der Voort ◽  
Thorbald van Hall ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Tumor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Normal Tissue ◽  
P53 Protein ◽  
P53 Gene ◽  
Wild Type ◽  
Wild Type P53 ◽  
Tumor Outgrowth ◽  
Tumor Eradication

The tumor suppressor protein p53 is overexpressed in close to 50% of all human malignancies. The p53 protein is therefore an attractive target for immunotherapy. Cytotoxic T lymphocytes (CTLs) recognizing a murine wild-type p53 peptide, presented by the major histocompatibility complex class I molecule H-2Kb, were generated by immunizing p53 gene deficient (p53 −/−) C57BL/6 mice with syngeneic p53-overexpressing tumor cells. Adoptive transfer of these CTLs into tumor-bearing p53 +/+ nude mice caused complete and permanent tumor eradication. Importantly, this occurred in the absence of any demonstrable damage to normal tissue. When transferred into p53 +/+ immunocompetent C57BL/6 mice, the CTLs persisted for weeks in the absence of immunopathology and were capable of preventing tumor outgrowth. Wild-type p53-specific CTLs can apparently discriminate between p53-overexpressing tumor cells and normal tissue, indicating that widely expressed autologous molecules such as p53 can serve as a target for CTL-mediated immunotherapy of tumors.

scholarly journals Chemotherapy-induced immunogenic modulation of tumor cells enhances killing by cytotoxic T lymphocytes and is distinct from immunogenic cell death

2013 ◽  
Vol 133 (3) ◽  
pp. 624-636 ◽  
Author(s):  
James W. Hodge ◽  
Charlie T. Garnett ◽  
Benedetto Farsaci ◽  
Claudia Palena ◽  
Kwong-Yok Tsang ◽  
...  
Keyword(s):  
Cell Death ◽  
T Lymphocytes ◽  
Tumor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Immunogenic Cell Death ◽  
Immunogenic Modulation

Frequency analysis of tumor-reactive cytotoxic T lymphocytes in peripheral blood of a melanoma patient vaccinated with autologous tumor cells

1994 ◽  
Vol 39 (2) ◽  
pp. 93-99 ◽  
Author(s):  
Wolfgang Herr ◽  
Thomas W�lfel ◽  
Michael Heike ◽  
Karl-Hermann Meyer zum B�schenfelde ◽  
Alexander Knuth
Keyword(s):  
T Lymphocytes ◽  
Tumor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Frequency Analysis ◽  
Peripheral Blood ◽  
Melanoma Patient ◽  
Autologous Tumor

Frequency analysis of tumor-reactive cytotoxic T lymphocytes in peripheral blood of a melanoma patient vaccinated with autologous tumor cells

1994 ◽  
Vol 39 (2) ◽  
pp. 93-99 ◽  
Author(s):  
Wolfgang Herr ◽  
Thomas W�lfel ◽  
Michael Heike ◽  
Karl-Hermann Meyer zum B�schenfelde ◽  
Alexander Knuth
Keyword(s):  
T Lymphocytes ◽  
Tumor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Frequency Analysis ◽  
Peripheral Blood ◽  
Melanoma Patient ◽  
Autologous Tumor

scholarly journals Dendritic cells matured with recombinant human sperm associated antigen 9 (rhSPAG9) induce CD4+, CD8+ T cells and activate NK cells: a potential candidate molecule for immunotherapy in cervical cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hemavathi Dhandapani ◽  
Hascitha Jayakumar ◽  
Abirami Seetharaman ◽  
Shirley Sunder Singh ◽  
Selvaluxmy Ganeshrajah ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
T Cells ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Tumor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Functional Characterization ◽  
Autologous Tumor ◽  
Potential Candidate ◽  
Antigenic Source

Abstract Background Dendritic cell (DC)-based immunotherapy is capable of activating the immune system and in particular tumor-specific cytotoxic T lymphocytes (CTLs) to eradicate the tumor. However, major limitations are the availability of autologous tumor cells as antigenic source and the selection of antigen that may have potential to activate both CD4+ and CD8+ T cells in immune-specific manner. Recently, we reported the expression of sperm associated antigen 9 (SPAG9) that is associated with various types of malignancies including cervical cancer. We examined the recombinant human SPAG9 (rhSPAG9) as an antigenic source for generating efficient DCs to stimulate CD4+ and CD8+ T cell responses for future DCs-based vaccine trials in cervical cancer patients. Methods Human monocytes derived DCs were pulsed with different concentrations (250 ng/ml to 1000 ng/ml) of recombinant human SPAG9 (rhSPAG9) and evaluated for their phenotypic and functional ability. The efficacy of DCs primed with 750 ng/ml of rhSPAG9 (SPDCs) was compared with DCs primed with autologous tumor lysates (TLDCs), to induce CD4+, CD8+ T cells and activating NK cells. In addition, we investigated the effect of the chemotherapeutic drug cisplatin on phenotypic and functional potential of SPDCs. Results Phenotypic and functional characterization of DCs pulsed with 750 ng/ml rhSPAG9 was found to be optimal and effective for priming DCs. SPDCs were also capable of stimulating allogeneic T cells similar to TLDCs. SPDCs showed a statistically insignificant increase in the expression of maturation marker CD83 and migration towards CCL19 and CCL21 compared with TLDCs (CD83; P = 0.4; migration; P = 0.2). In contrast, although TLDCs showed better proliferation and secretion of Th1 cytokines (IL12p40, IL12p70 and IFNγ) compared to SPDCs, this difference was not statistically significant (IL12p40, P = 0.06). Further we also observed that clinical dose of cisplatin (200 µM) treated SPDCs were able to stimulate the proliferation of cytotoxic T lymphocytes without increasing the FOXP3+ Tregs in autologous co-cultures. Conclusions In summary, in order to overcome the limitation of the availability of autologous tumor cells as antigenic sources, our present strategy provides an insight to consider rhSPAG9 as a strong immunogen for DC-based immunotherapy for cervical cancer trials and warrants further studies. This is the first report to suggest that rhSPAG9 is an effective antigen for pulsing DCs that are capable of eliciting a potent Th1 response which, in turn, may help in decreasing the tumor burden when used along with a cisplatin based combinatorial regimen for therapeutic intervention.

Antitumor activity against established intracerebral gliomas exhibited by cytotoxic T lymphocytes, but not by lymphokine-activated killer cells

1992 ◽  
Vol 77 (5) ◽  
pp. 757-762 ◽  
Author(s):  
Frank P. Holladay ◽  
Teresa Heitz ◽  
Gary W. Wood
Keyword(s):  
Brain Tumor ◽  
T Lymphocytes ◽  
Tumor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Lak Cells ◽  
Lymphokine Activated Killer Cells ◽  
Killer Cells ◽  
Brain Tumor Cells

✓ Specific immune responses against malignant brain tumors have been difficult to demonstrate. Moreover, immunotherapy has met with little success, despite using lymphocytes with high levels of cytotoxicity against brain tumor cells. Lymphokine-activated killer (LAK) cells that nonspecifically kill brain tumor cells are produced by stimulating resting precursors with high concentrations of interleukin-2 (IL-2). Cytotoxic T lymphocytes that specifically kill brain tumor cells are produced by stimulating antigen receptor-positive immune-cell precursors with tumor cells. In an attempt to gain insight into immune cell function against brain tumors, the present study compared the in vitro and in vivo activities of LAK cells and cytotoxic T lymphocytes produced against RT2, a fast-growing rat glioma cell line. Lymphokine-activated killer cells were produced by stimulating normal rat spleen cells with 1000 units of IL-2, and RT2-specifie cytotoxic T lymphocytes were produced by priming them in vivo with RT2 and Corynebacterium parvum and restimulating primed spleen cells with RT2 in vitro. Lymphokine-activated killer cells were highly cytotoxic for a panel of syngeneic and allogeneic brain tumor and non-brain tumor target cells, including RT2, as measured in a 4-hour 51Cr release assay. Cytotoxic T lymphocytes were highly cytotoxic only for syngeneic brain tumor target cells. Lymphokine-activated killer cells and cytotoxic T lymphocytes were tested for in vivo antitumor activity against intracerebral RT2 by intravenous adoptive transfer of activated lymphocytes. Untreated rats died in approximately 2 weeks. Lymphokine-activated killer cells plus IL-2 failed to affect survival when treatment was initiated as early as 1 day following tumor inoculation. Cytotoxic T lymphocytes and IL-2 administered as late as Day 5 rejected progressing intracerebral tumor. Thus, although both cytotoxic T lymphocytes and LAK cells exhibited high levels of in vitro killing of glioma cells, only cytotoxic T lymphocytes rejected progressing intracerebral tumors.

Generation of tumor-specific cytotoxic T-lymphocytes from peripheral blood of colorectal cancer patients for adoptive immunotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3056-3056
Author(s):  
Marco Bregni ◽  
Serena Del Bue ◽  
Andrea Galli ◽  
Alberto della Valle ◽  
Pasquale Ferrante ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Peripheral Blood ◽  
Tumor Cell Line ◽  
Interleukin 4 ◽  
Autologous Tumor ◽  
The Third ◽  
Ifn Γ

3056 Background: Adoptive T-cell transfer (ACT) using autologous TIL, grown ex vivo and then infused into the cancer patient after lymphoablative chemotherapy, has emerged as an effective treatment for patients with metastatic melanoma. However, this approach has been hampered by the difficulty of isolating TILs from tumors other than melanoma, and of amplifying a sufficient quantity of autologous tumor-reactive T cells. So we decided to adopt a recently described procedure for generating in vitro large numbers of anti-tumor HLA-restricted CTLs, by stimulating patient’s CD8-enriched peripheral blood mononuclear cells (PBMCs) with DCs pulsed with apoptotic solid tumor cells (TCs) as a source of tumor antigens. Methods: 61 patients affected by CRC were enrolled. Tumor biopsies were obtained at surgery, together with 100 ml of heparinized peripheral blood. Tumors were dissociated to a single-cell suspension and cultured in order to obtain tumor cell line from each patient. Dendritic cells (DCs) were generated from previously separated PBMCs, using a magnetic positive selection of CD14+ monocytes, cultured in presence of Interleukin-4 and recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). Anti-tumor cytotoxic T lymphocytes (CTLs) were elicited using DCs as antigen-presenting cells, autologous apoptotic tumor cells as source of antigens and T CD-8 lymphocytes enriched effectors, with weekly stimulation. To evaluate the cytotoxic activity of CTLs, interferon-γ (IFN-γ) secretion was assessed by ELISPOT. Results: Tumor cell lines and DCs were obtained from 19 out of 61 patients. ELISPOT was performed so far for 6 patients: strong IFN-γ secretion was detected at the third, fourth and fifth stimulations for one patient and at the second for another patient, whereas for three patients a weak secretion was detected during the second and the third stimulations. CTLs from one patient did not react to the stimulations. Conclusions: Generation of CTLs suitable for ACT immunotherapy is feasible from peripheral blood in patients with CRC.

Sign in / Sign up

Export Citation Format

Share Document