Pilot safety study of perivascular injection of tissue-engineered allogeneic aortic endothelial cells in patients undergoing minimally invasive peripheral revascularization.

Objective: Restenosis is a limitation of endovascular interventions performed in the superficial femoral artery (SFA). Preclinical studies have demonstrated that the perivascular delivery of tissue-engineered allogeneic aortic endothelial cells (PVS-10200) reduced stenosis in porcine models of SFA revascularization. The purpose of this study was to investigate the safety and feasibility of percutaneous PVS-10200 delivery after angioplasty and stenting in the SFA of patients with peripheral artery disease.

Antitumor activity of a human cytotoxic T-cell line (TALL-104) in brain tumor xenografts.

Malignant glioma in adults and primitive neuroectodermal tumors/medulloblastomas in children are the most common malignant primary brain tumors that either respond poorly to current treatment or tend to recur. Adoptive therapy with TALL-104 cells-an IL-2-dependent, major histocompatibility complex nonrestricted, cytotoxic T-cell line-has demonstrated significant antitumor activity against a broad range of implanted or spontaneously arising tumors. This study investigates distribution of systemically and locally administered TALL-104 cells and their efficacy in effecting survival of a rat model of human brain tumor.

N-(n-Benzylpiperidin-4-yl)-2-[18F]fluorobenzamide: a potential ligand for PET imaging of breast cancer.

N-(N-Benzylpiperidin-4-yl)-2-[(18)F]fluorobenzamide (2), a potential ligand for PET imaging of sigma receptor, has been found to be a potential agent for detection of breast cancer. In vivo studies in severe combined immunodeficient (SCID) mice bearing MDA-MB231 tumors showed that the uptake of compound 2 in these tumors was high (3.8%/g); the ratios of tumor/muscle and tumor/blood were 6.

The human leukemic T-cell line, TALL-104, is cytotoxic to human malignant brain tumors and traffics through brain tissue: implications for local adoptive immunotherapy.

Preclinical studies with the human MHC nonrestricted cytotoxic T-cell leukemic line, TALL-104, were performed in anticipation of its use in cellular immunotherapy trials for primary malignant brain tumors. In this study, we have: (a) quantitated the in vitro brain tumor cell lysis; (b) measured the cytokine secretion upon coincubation of TALL-104 cells with brain tumor cells; (c) investigated the effect of dexamethasone on brain tumor cell cytolysis by TALL-104 cells; (d) explored the effects of lethal irradiation and cryopreservation on TALL-104 cell viability and lytic efficacy; and (e) estimated the damage TALL-104 cells induce to murine normal and tumor brain cells and their trafficking patterns in both normal and tumor-bearing rat brain upon intracranial infusion. In vitro coincubation of TALL-104 cells with human brain tumor cells, explants, and cell lines resulted in significant lysis of them, but normal brain cells were spared.

Phase I trial of TALL-104 cells in patients with refractory metastatic breast cancer.

The human cytotoxic T-cell line TALL-104 displays antitumor effects in animals with implanted and spontaneous malignancies. A Phase I trial was conducted to determine toxicity of TALL-104 cell therapy in women with metastatic refractory breast cancer. Fifteen patients with metastatic infiltrating ductal (n = 12), lobular (n = 2), or medullary (n = 1) carcinoma received escalating doses of lethally irradiated TALL-104 cells (three patients/group received 10(6), 3 x 10(6), 10(7), 3 x 10(7), and 10(8) cells/kg) for 5 consecutive days (induction course).

Adoptive therapy of canine metastatic mammary carcinoma with the human MHC non-restricted cytotoxic T-cell line TALL-104.

Adoptive transfer of human TALL-104 killer cells into a dog with metastatic mammary adenocarcinoma resulted in 50% reduction of the largest lung metastasis and stabilization of the other lesions for 10 weeks, accompanied by the development of tumor-specific immune responses. Upon halting cell therapy, the dog developed new lung lesions within 10 weeks and died of slowly progressive disease. TALL-104 cell therapy of mice bearing the dog's tumor xenograft induced 65% reduction of local tumor growth and regression of lung metastases in 100% of the animals.

Adjuvant treatment of canine osteosarcoma with the human cytotoxic T-cell line TALL-104.

The human cytotoxic T-cell line TALL-104 has been used successfully to treat cancer in experimental mouse models with implanted tumors and in dogs with spontaneously occurring malignancies. This study investigated the efficacy of TALL-104 cells given in an adjuvant setting to dogs with appendicular osteosarcoma after surgery and chemotherapy. Of the 23 dogs enrolled in the study, 20 had undergone amputation of the affected limb, and 3 had undergone limb salvage surgery.

Biodistribution of human MHC non-restricted TALL-104 killer cells in healthy and tumor bearing mice.

The human cytotoxic T cell line TALL-104 displays potent anti-tumor effects in animals with spontaneous and induced malignancies. We investigated the biodistribution of TALL-104 cells in tumor bearing and healthy mice. 111In-labeled TALL-104 cells, injected intravenously, localized primarily in the lungs for the first 2 h, and redistributed to liver, spleen, and kidneys in the following 24 h both in immunodeficient and immunocompetent mice.

Effects of development of host immunity on the biodistribution of xenogeneic MHC non-restricted cytotoxic T cells: implications for adoptive cell therapy of cancer.

The human MHC non-restricted cytotoxic T cell line TALL-104 has potent anti-tumor effects in dogs with spontaneous tumors. This study was designed to examine the effects of the development of host immune responses on the baseline organ distribution of TALL-104 cells in healthy dogs. 111In-oxine labeled TALL-104 cells (107 cells/kg) were infused systemically in three dogs, either on day 1, 3, or 5 of a 5-day injection cycle; two dogs received two more injections of the labeled cells at monthly intervals, whereas the third dog received free 111In-oxine, 3 months after the first 5-day infusion.

Cell therapy of a highly invasive human breast carcinoma implanted in immunodeficient (SCID) mice.

Although enormous progress has been made in the detection and treatment of localized (nonmetastatic) breast cancer, there has been relatively moderate progress toward the effective treatment of advanced disease. This study investigates the antitumor efficacy of a potent MHC nonrestricted cytotoxic human T cell line (TALL-104) upon transfer into a clinically relevant mouse model of metastatic breast cancer. Fragments from a surgical specimen of a patient with infiltrating ductal carcinoma were implanted s.

Successful treatment of canine malignant histiocytosis with the human major histocompatibility complex nonrestricted cytotoxic T-cell line TALL-104.

The human MHC nonrestricted cytotoxic T-cell line TALL-104 exerts potent antitumor effects in animal models with both induced and spontaneous cancers. The present report documents the ability of systemically delivered TALL-104 cells to induce durable clinical remissions in four of four dogs with malignant histiocytosis (MH). The animals received multiple i.

TALL-104 cell therapy of human solid tumors implanted in immunodeficient (SCID) mice.

We have developed a novel approach to adoptive therapy of cancer based on the use of a human T cell line (TALL-104) which is endowed with major histocompatibility complex non-restricted cytotoxic activity against a broad range of tumors and across several species, while sparing cells from normal tissues. The present study investigates the efficacy of TALL-104 cell therapy in severe combined immunodeficient (SCID) mice implanted with human solid tumors. The human cell lines DU-145 (prostate cancer), A549 (lung carcinoma) and WM451 (melanoma) were implanted subcutaneously (s.

Opposite effects of linoleic acid and conjugated linoleic acid on human prostatic cancer in SCID mice.

The relationship between dietary fat intake (level and type) and cancer development is a matter of concern in Western society. The purpose of this study was to determine the effect of three different diets on the local growth and metastatic properties of DU-145 human prostatic carcinoma cells in severe combined immunodeficient (SCID) mice. Animals were fed a standard diet or diets supplemented with 1% LA or 1% CLA for 2 weeks prior to subcutaneous (s.

Growth characteristics and metastatic properties of human breast cancer xenografts in immunodeficient mice.

We evaluated the growth and metastatic potential of two human breast cancer cell lines and 16 patient-derived biopsy specimens, representing the most common histological types of breast carcinomas, upon subcutaneous implantation into severe combined immunodeficient (SCID) mice. The method of engraftment we used, based on implantation of intact tissue specimens and complete immunosuppression of the host, provided an easier system to grow human breast carcinoma specimens in mouse models and resulted in a 50% success rate of tumor take. No correlation was found between growth in SCID mice and pathological diagnosis, grading, or estrogen/progesterone receptor expression by the tumor biopsy specimen.

Role of CD38 and its ligand in the regulation of MHC-nonrestricted cytotoxic T cells.

Human CD38 is a type II transmembrane glycoprotein that regulates lymphocyte adhesion, proliferation, and cytokine production. The mAb Moon-1 recognizes a ligand for CD38 (CD38L) and specifically inhibits CD38-mediated cell adhesion. To analyze the role of CD38 and its ligand in MHC-nonrestricted T cell activation, we examined the effects of Moon-1 and the anti-CD38 mAb IB4 on the effector functions of the IL-2-dependent T cell line TALL-104 (CD3/TCR-alphabeta+, CD8+, CD56+) and of LAK cells (90% CD3+).

Synergistic effects of adriamycin and TALL-104 cell therapy against a human gastric carcinoma in vivo.

The single and combined antitumor effects of adriamycin and a major histocompatibility complex non-restricted human cytotoxic T cell line (TALL-104) were evaluated in severe combined immunodeficient (SCID) mice engrafted subcutaneously with a biopsy sample from a patient with a highly metastatic gastric carcinoma. Chemotherapy was initiated 3 weeks after tumor implantation, when local growth was advanced, and consisted of 2 weekly injections of adriamycin. gamma-irradiated (40 Gy) TALL-104 cells were administered daily for 2 weeks, starting 1 day after the end of chemotherapy.

Toxicological and immunological evaluation of the MHC-non-restricted cytotoxic T cell line TALL-104.

The human MHC-non-restricted cytotoxic T cell line TALL-104 has been shown to display potent antitumor effects in several animal models with spontaneous and induced malignancies. In view of its potential future use in cancer therapy, we investigated the tolerability and target-organ toxicity of these cells in various animal species. The acute toxicity of TALL-104 cell administrations was evaluated in: (a) healthy immunocompetent mice and immunodeficient (SCID) mice bearing human tumors using multiple (up to 15) intraperitoneal (i.

Conjugated linoleic acid suppresses the growth of human breast adenocarcinoma cells in SCID mice.

Conjugated linoleic acid (CLA), which is mainly derived from dairy products, has been shown both in vitro and in animal models to have strong anti-tumor activity. Particular effects were observed on the growth and metastatic spread of transplantable mammary tumors. In this study, we examined the effect of dietary CLA on the growth of human breast adenocarcinoma cells in severe combined immunodeficient (SCID) mice.

Antitumor efficacy of a human major histocompatibility complex nonrestricted cytotoxic T-cell line (TALL-104) in immunocompetent mice bearing syngeneic leukemia.

The human MHC nonrestricted cytotoxic T-cell line TALL-104 displays potent tumoricidal activity both in vitro and in animals bearing either spontaneous or induced tumors. In the present study, we used B6D2F1 mice engrafted with the syngeneic pre-B leukemia cell line 7OZ as a model system to investigate the mechanisms by which TALL-104 cells display antitumor activity in an immunocompetent host. In vitro studies indicated that 7OZ cells are resistant to TALL-104 cell-induced necrotic death, as measured in 51Cr release assays, but can be killed by the xenogeneic effectors via apoptotic mechanisms.

Phase I clinical trial with a human major histocompatibility complex nonrestricted cytotoxic T-cell line (TALL-104) in dogs with advanced tumors.

The human TALL-104 cell line is endowed with a uniquely potent MHC nonrestricted tumoricidal activity across several species. In view of the potential applicability of TALL-104 cells as an anticancer agent, this study was conducted to evaluate the possible toxicity and efficacy of this new cell therapy in a superior animal model with spontaneous tumors. Nineteen canine cases with advanced, refractory malignancies of various histological types were entered in the study.

Use of a lethally irradiated major histocompatibility complex nonrestricted cytotoxic T-cell line for effective purging of marrows containing lysis-sensitive or -resistant leukemic targets.

Improved marrow purging protocols are needed in autologous bone marrow transplantation (BMT) to achieve complete eradication of minimal residual disease. This study investigates the potential of a human major histocompatibility complex (MHC) nonrestricted killer T-cell line (TALL-104) as a new marrow purging agent in a clinical setting. TALL-104 cells can be irradiated without losing cytotoxic activity against tumor targets in vitro.

A revertant TCR gamma delta + cell clone which has lost MHC nonrestricted cytotoxic activity but retains redirected killing upon stimulation of the CD3 receptor.

A variant nonkiller (K-) T-cell clone derived from the MHC nonrestricted killer (K+) cell line TALL-103/2 (CD3/TCR gamma delta +) was studied to determine whether its lytic defects were at the tumor-binding or post-binding level. The two TALL-103/2 clones were found to display similar mRNA expression of TCR/CD3 complex epsilon, zeta, gamma, and delta chains, and the same mRNA and protein levels of SRC-like protein tyrosine kinase and kinase activity. However, the K- cells express much less surface CD45 RA and contain smaller intracytoplasmatic cytotoxic granules with a lower expression of the TIA-1 protein.

Effects of lethal irradiation and cyclosporin A treatment on the growth and tumoricidal activity of a T cell clone potentially useful in cancer therapy.

The TALL-104 cell line, originally derived from a patient with T cell leukemia, can be maintained indefinitely in culture in the presence of interleukin-2 (IL-2) and is endowed with a highly potent major-histocompatibility-complex (MHC)-non-restricted tumoricidal activity both in vitro and in animal models. The present study analyzes in detail the short- and long-term effects of irradiation and cyclosporin A (CsA) treatment on the growth and tumoricidal function of this T cell clone as compared to polyclonal lymphokine-activated killer (LAK) cell preparations from healthy donors. DNA and RNA syntheses by both TALL-104 and LAK cells were irreversibly arrested a few hours after irradiation with 40 Gy.

Treatment of experimental glioblastoma with a human major histocompatibility complex nonrestricted cytotoxic T cell line.

This study investigates a new approach to adoptive therapy of glioblastoma using as antitumor effector a potent major histocompatibility complex nonrestricted killer clone (TALL-104) established from a patient with acute T-lymphoblastic leukemia. The human glioblastoma cell line U-87 MG could be successfully engrafted in mice with severe combined immunodeficiency using the i.p.

Reversal of acute myelogenous leukemia in humanized SCID mice using a novel adoptive transfer approach.

Advanced human malignancies cannot be permanently cured by adoptive transfer of autologous lymphokine-activated killer (LAK) cells. Moreover, administration of high doses of IL-2 to maintain LAK activity in vivo is associated with severe toxicity. In this study, we tested the anti-tumor efficacy of a uniquely potent MHC non-restricted human killer T cell clone (TALL-104) in humanized severe combined immunodeficient (SCID) mice bearing acute myelogenous leukemia (AML).