1) A paper describing the reduction of the immunogenicity of the murine anti-TAG 72 anti-tumor antibody, CC49, by CDR swapping has been published (a collaboration with S.V.S.Kashmiri and J.Schlom, NCI).2) A paper describing the further reduction of the immunogenicity of antibody CC49, by retaining only the specificity-determining residues has been published (a collaboration with S.V.S.Kashmiri and J.Schlom, NCI).3) A paper describing the construction of a single-chain tetravalent humanized antibody CC49 has been published (a collaboration with S.V.S.Kashmiri and J.Schlom, NCI).4) A paper hypothesizing the possible role of an alternative initiation site for mRNA translation in the pathology of Huntington's disease has been published.5) A paper describing the generation of a minimally immunogenic variant of humanized antibody CC49, has been submitted (a collaboration with S.V.S.Kashmiri and J.Schlom, NCI).6) Variants of humanized antibody CC49, in which the murine framework residues which had been retained during humanization are replaced with human amino acids, have been produced and have been shown to have antigen binding activity (a collaboration with S.V.S.Kashmiri and J.Schlom, NCI). These variants are expected to have minimal immunogenicity in human patients.7) A paper describing several humanized variants of the murine anti-CEA anti-tumor antibody, COL-1, is in preparation (a collaboration with S.V.S.Kashmiri and J.Schlom, NCI).8) Variants of antibody COL-1, in which the murine framework residues which had been retained during humanization are replaced with human amino acids, are being produced (a collaboration with S.V.S.Kashmiri and J.Schlom, NCI).9) A single-chain humanized CC49 Fv, suitable for conjugation to PEG-liposomes, has been generated. The immunoliposomes will be used to deliver cytotoxic molecules selectively to TAG 72-bearing cancer cells (a collaboration with the Antibody and Molecular Oncology Researchers group in the Philippines).10) A construct of human IgE fitted with humanized CC49 variable domains has been made. This molecule will be used to elicit IgE effector function against TAG 72-bearing cancer cells (a collaboration with B.A.Helm, Sheffield, UK).
