The immunotherapeutic potential of activated canine alveolar macrophages and antitumor monoclonal antibodies in metastatic canine melanoma.

A variety of immune cell activators can enhance the cytotoxic effects of monocytes/macrophages including interferon-gamma (IFN-gamma) and muramyl peptides, which are under investigation for cancer therapy in humans and dogs. Pulmonary alveolar macrophages (PAMs) in particular, are strategically located within the lung and provide a potential defense against cancer cells metastatic to the lung. For this reason, we examined the in vitro cytotoxic potential of fresh and IFN-gamma-activated PAMs from normal dogs targeted to canine malignant melanoma cells with antiganglioside monoclonal antibodies (mAbs).

Functional interleukin-2 receptors are expressed on natural killer-like leukemic cells from a dog with cutaneous lymphoma.

We identified a dog with large granular lymphocytic leukemia and cutaneous lymphoma that exhibited constitutive expression of interleukin-2 (IL-2) receptors by the leukemic peripheral blood lymphocytes. The leukemic cells phenotypically resembled natural killer (NK) cells, and their surface IL-2 receptors were functional, as determined by the capacity to bind human recombinant IL-2 with high-affinity resulting in the transduction of proliferation signals and in the development of lymphokine-activated killer cell activity. These cells produced IL-2 spontaneously, and they may have maintained their proliferative state through an IL-2-dependent autocrine growth pathway.

Differential cell analysis and phenotypic subtyping of lymphocytes in bronchoalveolar lavage fluid from clinically normal dogs.

In 33 healthy dogs, 66 bronchoalveolar lavage samples from the right and left caudal lung lobes were analyzed for volume of return, cellularity, differential cellularity, and immunophenotypic lymphocyte subpopulations. Lavage return was 64.8% (mean) following 3 sequential 25-ml lavages, for a total lavage volume of 75 ml.

Acute effects of continuous infusions of human recombinant interleukin-2 on serum thyroid hormone concentrations in dogs.

The effect of human recombinant interleukin-2 (IL-2) on serum thyroid hormone concentrations in dogs was studied. Four normal adult dogs received two consecutive weekly cycles of continuous infusions of 3 x 10(6) U m-2 daily for four days per week (days 1 to 4 and 8 to 11). The serum concentrations of IL-2, thyroxine (T4) and 3, 5, 3'-triiodothyronine (T3) were measured before and on days 2, 3 and 4, and 9, 10 and 11 of the infusions.

Potential to involve multiple effector cells with human recombinant interleukin-2 and antiganglioside monoclonal antibodies in a canine malignant melanoma immunotherapy model.

Human tumors originating from neuroectodermal cells such as malignant melanoma and neuroblastoma express high levels of disialogangliosides GD2 and GD3, making these antigens ideal for targeting by monoclonal antibodies (Mabs). The purpose of this study was to investigate expression and targeting of gangliosides on canine melanoma. Using immunohistochemical methods, we analyzed the expression of disialogangliosides GD2 and GD3 on canine oral malignant melanomas with murine Mabs 14.

Clinical and immunological effects of human recombinant interleukin-2 given by repetitive weekly infusion to normal dogs.

Four normal adult dogs received two consecutive weekly cycles of human recombinant interleukin-2 (IL-2) by continuous infusion for 4 days/week. The dose of IL-2 given to each dog was 3 x 10(6) units m-2 day-1. Toxicities consisted of mild vomiting, diarrhea, and lethargy to varying degrees in all the dogs.

Induction of lymphokine-activated killer (LAK) activity in canine lymphocytes with low dose human recombinant interleukin-2 in vitro.

Interleukin-2 (IL-2) is an immunostimulatory cytokine that induces activation of peripheral blood lymphocytes (PBL) which can mediate augmented tumor cytotoxicity. Several regimens using IL-2 as treatment for metastatic melanoma and renal carcinoma have shown measurable tumor responses in 10-20% of human patients. Our overall goals are to determine the efficacy of IL-2 as an adjuvant treatment for canine tumors.

High-dose UV-B radiation alters human dendritic cell costimulatory activity but does not allow dendritic cells to tolerize T lymphocytes to alloantigen in vitro.

Human blood dendritic cells require UV-B radiation (290 to 320 nm) in excess of 1,000 J/m2 to inhibit their stimulation of primary T-cell responses to alloantigen by 60% to 70% or more. The effect is twofold to threefold greater in the allogeneic mixed leukocyte reaction (MLR) than in polyclonal mitogenesis using comparable numbers of dendritic cells and doses of UV-B radiation. UV-B radiation does not significantly alter dendritic cell viability at the doses administered.

Methimazole as a protectant against cisplatin-induced nephrotoxicity using the dog as a model.

The protective effect of methimazole, a commonly used antithyroid drug, on cisplatin-induced nephrotoxicity was studied. Eight dogs received 80 mg/m2 cisplatin i.v.

The B7/BB1 antigen provides one of several costimulatory signals for the activation of CD4+ T lymphocytes by human blood dendritic cells in vitro.

T cells respond to peptide antigen in association with MHC products on antigen-presenting cells (APCs). A number of accessory or costimulatory molecules have been identified that also contribute to T cell activation. Several of the known accessory molecules are expressed by freshly isolated dendritic cells, a distinctive leukocyte that is the most potent APC for the initiation of primary T cell responses.