Sloan-kettering Institute for Cancer Research

Memorial Sloan Kettering Cancer Center

Other

Bo Dupont

Yasuo Morishima

Nancy Collins

Kenneth O Lloyd

Shun-ichiro Ogata

Richard John O'Reilly

Aisha Nasreen Hasan

Maria I New

Annamalai Selvakumar

Masahide Kobayashi

Soo Y Yang

Michael K Hoffman

Kazuyuki Naito

Robert W Knowles

Perrin C White

Xiao-Rong Liu

Provided herein are methods of generating antigen-specific T cells for therapeutic administration to a human patient having or suspected of having a pathogen or cancer, utilizing soluble IL-15/IL-15Rα complexes ex vivo, in cell culture during ex vivo sensitizing of T cells to the antigen or during ex vivo culturing of antigen-specific T cells. Also disclosed are antigen-specific T cells generated by such methods, and methods of treating a human patient using such antigen-specific T cells. Cell culture systems comprising human T cells, antigen-presenting cells, and soluble IL-15/IL-15Rα complexes are also provided.

Use of the IL-15/IL-15Rα complex in the generation of antigen-specific T cells for adoptive immunotherapy

This invention concerns a new monoclonal antibody (mAb) 4C, recognizing a specific antigen, Leu 200, found in human hematopoietic tissues. The monoclonal antibody precipitates a series of glycoproteins (Leu 200) with a molecular weight range of about 190,000 to 230,000 from both T- and B-cell lines. The series of glycoproteins resolves into four discrete glycoprotein bands, the distribution of which varies according to the cell lines. Bands 3 and 4 predominate in a majority of T-cells whereas band 2 predominates in B cells. Thus, a Leu 200 antigen subset distribution is possible with mAb 4C. Bands 1, 2, 3, 4 have apparent molecular weights of 230K, 215K, 205K, and 190K respectively, with differences in their carbohydrate moieties. nAb 4C is a IgG sub two a,kappa immunoglobulin. 4C has potential use in leukemia, hematopoietic cell differentiation and transplantation diagnoses and therapy.

Monoclonal antibody for human hematopoietic glycoproteins and method

A cDNA clone is isolated encoding a bovine adrenal cytochrome P-450 specific for steroid 21-hydroxylation (P-450.sub.C21). This plasmid pC21a contains an insert of 520 base pairs. It hybridizes with mRNA encoding P-450.sub.C21. The peptide encoded by the insert is highly homologous to two peptides isolated from porcine P-450.sub.C21 and shows limited homology to the P-450 induced by phenobarbital in rat liver. This probe and its human equivalents can be used to screen in utero i.e. pre-natal as well as post-natal patients for adrenal hyperplasia since it reacts well with human DNA as shown. These probes can also be useful for an industrial fermentation process to produce cortisone in quantity.

Genetic probe used in the detection of adrenal hyperplasia

This invention concerns a new monoclonal antibody (mAb) 4C, recognizing a specific antigen, Leu 200, found in human hematopoietic tissues. The monoclonal antibody precipitates a series of glycoproteins (Leu 200) with a molecular weight range of about 190,000 to 230,000 from both T- and B-cell lines. The series of glycoproteins resolves into four discrete glycoprotein bands, the distribution of which varies according to the cell lines. Bands 3 and 4 predominate in a majority of T-cells whereas band 2 predominates in B cells. Thus, a Leu 200 antigen subset distribution is possible with mAb 4C. Bands 1, 2, 3, 4 have apparent molecular weights of 230K, 215K, 205K, and 190K respectively, with differences in their carbohydrate moieties. mAb 4C is a IgG sub two a, kappa immunoglobulin. 4C has potential use in leukemia, hematopoietic cell differentiation and transplantation diagnoses and therapy.

A monoclonal antibody 4A produced by a human-mouse hybridoma cell line is described. In the presence of complement, 4A subsets both cytotoxic and helper T cells creating a diagnostic tool in blood biochemistry.

Monoclonal antibody subsetting human helper and killer T-cells and method

Two monoclonal antibodies (3-3 and 3-40) were produced which identify two new leukemia associated antigens. Both antibodies reacted with most cell lines derived from patients with T lymphoblastic leukemia (T-ALL), but were not detected on suspensions of normal hematopoietic cells, including thymocytes, by cytotoxicity, absorption of indirect immunofluorescence assays. Analysis of fresh leukemic cells indicated that mAb 3-3 only reacted with T-ALL cells, while mAb 3-40 reacted with some non-T non-B ALL cells and a few acute myelocytic leukemia (AML) cells, as well as T-ALL cells. The 3-40 antigen was also found histopathologically in frozen sections of several normal tissues, including the epithelial cells and a few lymphoid cells of the thymus, and some malignant tissues, while the 3-3 antigen was not found in any tissue studied. A 'double absorption' assay provided additional serological evidence the the two antibodies identify different antigenic determinants. Biochemical analysis indicated that the molecules immunoprecipitated by mAb 3-3 and mAb 3-40 have molecular weights of 35-40,000 daltons. It is demonstrated that the 3-3 and 3-40 antigens are markers for human T-ALL and can be used along with the normal T lymphocyte antigen, 3A1, to discriminate T-ALL from cutaneous T-cell lymphoma (CTCL), adult T cell leukemia (ATL) and T cell chronic lymphocytic leukemia (T-CLL).

Method for differential diagnosis of T cell leukemias using monoclonal

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Harrison, NY, United States of America

Bo Dupont