http://hdl.handle.net/1721.1/7787 Fri, 24 May 2013 13:49:19 GMT 2013-05-24T13:49:19Z http://hdl.handle.net/1721.1/77762 Studies in the revulcanization of reclaim rubber Roboff, Stanley B Thesis (B.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1943.; MIT copy bound with: The use of scrap leather for artificial leather soles / Alfred B. Babcock, Jr. and William R. Kittredge. 1943.; Includes bibliographical references (leaves 20-21). Fri, 01 Jan 1943 00:00:00 GMT http://hdl.handle.net/1721.1/77762 1943-01-01T00:00:00Z http://hdl.handle.net/1721.1/77761 Absorption coefficients in light oil scrubbers Forbes, Edward Colin; Kao, John Yü-Ling Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1941.; Includes bibliographical references (leaf 91). Wed, 01 Jan 1941 00:00:00 GMT http://hdl.handle.net/1721.1/77761 1941-01-01T00:00:00Z http://hdl.handle.net/1721.1/76957 Engineering persistent interleukin-2 for cancer immunotherapy Gai, Shuning Mobilizing the immune system to recognize and destroy tumor cells is a promising strategy for treating cancer. In contrast to standard therapeutic approaches such as surgery, radiation, and chemotherapy, immunotherapy offers the possibility of systemic yet tumor-specific cell killing as well as long-lasting cancer protection. A significant mode of tumor rejection is direct tumor cell killing by immune cells, such as cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. These cell types are stimulated to proliferate by the cytokine interleukin-2 (IL-2). Consequently, IL-2 has been actively pursued as an agent for immunotherapy, either alone or in combination with other therapeutic strategies. IL-2 is characterized by rapid systemic clearance, with a fast-phase serum half-life of 13 minutes and a slow-phase half-life of 85 minutes. We hypothesized that prolonging the persistence of IL-2 at the cell surface or extending its circulation lifetime would increase its immunostimulatory potency. Therefore, we evolved murine IL-2 to bind the alpha subunit of its receptor, known as IL-2Ra or CD25, with 500-fold higher affinity; tethered IL-2 to the surface of T cells via streptavidin sandwiches; and fused IL-2 to the antibody Fc fragment, designated Fc/ IL-2, which extended the slow-phase serum half-life by 15 hours. Compared to free IL-2, Fc/IL-2 fusions induced superior control of solid tumors in mice. Interestingly, combining Fc/IL-2 with an anti-tumor antibody led to potent suppression of tumor growth during treatment. Furthermore, combination therapy protected two of three mice from subsequent tumor re-challenge. Depletion of CTLs or NK cells completely or partially, respectively, abrogated treatment efficacy, suggesting these immune cell types contribute to the anti-tumor response. In the context of Fc fusion, increasing the affinity of IL-2 for CD25 did not further improve efficacy. Ablation of CD25 binding, however, significantly reduced efficacy and also increased treatment toxicity. Since we employed a mutant Fc with disrupted FcyR binding, and hence reduced effector function, and fused IL-2 to mutant Fc monovalently, the significant therapeutic benefit of Fc/IL-2 over free IL-2 likely results from the extension of IL-2 circulation lifetime. We hypothesize that long-circulating IL-2 would potently synergize with other anti-tumor antibodies for effective cancer immunotherapy. Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2012.; Cataloged from PDF version of thesis.; Includes bibliographical references (p. 102-109). Sun, 01 Jan 2012 00:00:00 GMT http://hdl.handle.net/1721.1/76957 2012-01-01T00:00:00Z http://hdl.handle.net/1721.1/76904 Biomaterials for protection and repair of the central nervous system Pritchard, Christopher D., (Christopher David) An injectable hydrogel for controlled release of methylprednisolone was designed based on the inflammatory response during acute spinal cord injury. The gel is injectable through a small gauge needle, cross-links under physiological conditions, and releases methylprednisolone over a time period on the order of weeks. Swelling properties were characterized to address potential safety concerns for potential clinical use. Two studies are presented towards the development of a model Brown-Sequard syndrome and accompanying behavioral and pathological outcome measures for evaluation of biomaterials in vivo. A modified poly(glycerol-co-sebacic acid) membrane was developed using electrospun poly(s-caprolactone) nanofibers. Retinal adhesion and histology was evaluated in vitro. Membranes were evaluated in vivo for their ability to selectively remove photoreceptors in situ and promote survival and integration of retinal transplants. Viscoelastic poly(ethylene glycol) sols were evaluated as potential vitreous substitutes. Finally, a business plan outlines the strategy towards clinical trials for a hydrogel vitreous substitute. Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2012.; "June 2012." Cataloged from PDF version of thesis.; Includes bibliographical references. Sun, 01 Jan 2012 00:00:00 GMT http://hdl.handle.net/1721.1/76904 2012-01-01T00:00:00Z