Richard G. Lynch

Augmentation of murine immune responses by amphotericin b.

Abstract Immunostimulant effects have been demonstrated in mice following single injections of amphotericin B or amphotericin methyl ester. Augmentation of both humoral and cell-mediated immune responses helps to explain the beneficial therapeutic effects observed in human and murine neoplasms after administration of amphotericin. Relevant to its immunological adjuvant properties, amphotericin produces striking reversible changes in murine thymus and splenic weights and in lymphoid organ histology. The chemical purity, nonimmunogenicity, and permissible toxicity of amphotericin recommend it as a model for the study of the cellular and molecular mechanisms of immunological adjuvants.

Plasmacytoma spleen colonization: A sensitive, quantitative in vivo assay for idiotype-specific immune suppression of MOPC-315

A spleen colony-forming assay for the measurement of idiotype-specific transplantation resistance to MOPC-315 is described. The assay is highly quantitative, sensitive, reproducible, less time consuming and distinctly superior to conventional in vivo assays which measure tumor incidence, tumor size, and/or host survival time after tumor challenge. The assay directly measures those clonogenic cells of the MOPC-315 myeloma which have a sufficient proliferative capacity to form macroscopic splenic foci within 14 days after intravenous challenge.

Regulation of Murine Myeloma Cell Growth and Differentiation: Cellular and Molecular Mechanisms, and Therapeutic Implications

Publisher Summary This chapter presents previous studies which established the following: (1) murine myeloma cells differentiate during in vivo growth, (2) myeloma cell growth and differentiation can be regulated by the myeloma-bearing host, and (3) myeloma cell regulation is effected by experimentally focusing onto the malignant antibody-producing cells components of the immunoregulatory apparatus that ordinarily are targeted to nonneoplastic B cells. These findings with murine myeloma raise the possibility that neoplastic B cells in humans may be amenable to therapeutic control using an immunoregulatory approach. As normal plasma cells are the differentiated progeny of nonsecretory B lymphocytes that synthesize antibody and incorporate it into their cell surface membranes, the possibility that secretory myeloma cells might be derived from nonsecretory precursors was considered and the idiotype-specific myeloma transplantation resistance was mediated at the level of a nonsecretory myeloma cell. Inherent in such a scheme was the assumption that myeloma cells were heterogeneous and that they differentiated during in vivo growth. To determine whether myeloma cells differentiated, the growth, morphology, and immunoglobulin expression of MOPC-315 cells enclosed in Millipore diffusion chambers implanted into the peritoneal cavities of normal mice was monitored.