The United States of America, As Represented by the Secretary, Department of Health and Human Services

Nan Li

Mitchell Ho

Ira H Pastan

Dimiter Stanchev Dimitrov

Dan Li

Jiajia Pan

Jessica D Hong

Bryan D Fleming

Camel single-domain monoclonal antibodies that specifically bind human and mouse mesothelin are described. Chimeric antigen receptor (CAR) T cells and antibody conjugates based on the mesothelin-specific antibodies are also described. The disclosed CAR T cells, mesothelin-specific antibodies and conjugates thereof can be used, for example, in the diagnosis or treatment of mesothelin-positive cancers.

Cross species single domain antibodies targeting mesothelin for treating solid tumors

Monoclonal antibodies that specifically bind glypican-1 (GPC1) are described. Chimeric antigen receptor (CAR) T cells, immunotoxins and other antibody conjugates based on the GPC1-specific antibodies are also described. The disclosed CAR T cells, immunotoxins, GPC1-specific antibodies and conjugates thereof can be used, for example, in the diagnosis or treatment of GPC1-positive pancreatic cancer and other cancers.

High affinity monoclonal antibodies targeting glypican-1 and methods of use

Monoclonal antibodies that bind glypican-2 (GPC2) with high affinity are described. Immunotoxins and chimeric antigen receptors (CARs) that include the disclosed antibodies or antigen-binding fragments thereof are further described. In some instances, the antibody or antigen-binding fragment is humanized. The disclosed GPC2-specific antibodies and conjugates can be used, for example, for the diagnosis or treatment of GPC2-positive cancers, including neuroblastoma, medulloblastoma and retinoblastoma.

High affinity monoclonal antibodies targeting glypican-2 and uses thereof

Nucleic acid constructs encoding a chimeric antigen receptor (CAR) and a truncated human epidermal growth factor receptor (huEGFRt) are described. The encoded CARs include a tumor antigen-specific monoclonal antibody, such as a glypican-3 (GPC3)-specific, a GPC2-specific or a mesothelin-specific monoclonal antibody, fused to a CD8&#x3b1; hinge region, a CD8&#x3b1; transmembrane region, a 4-1BB co-stimulatory domain and a CD3&#x3b6; signaling domain. Isolated host cells, such as isolated T cells that co-express the disclosed CARs and huEGFRt are also described. T cells transduced with the disclosed CAR constructs can be used for cancer immunotherapy.

Chimeric antigen receptors targeting glypican-3 or mesothelin

A panel of human variable heavy (VH) single domain monoclonal antibodies specific for cell-surface glypican-2 (GPC2) are described. Methods for the diagnosis and treatment and GPC2-positive cancer are also described. Recombinant immunotoxins comprised of a GPC2-specific VH domain antibody and a clinically used form ofexotoxin A (PE38) were generated and shown to inhibit GPC2-positive neuroblastoma tumor cell growth and inhibit neuroblastoma xenograft growth in nude mice, without significant toxicity. Chimeric antigen receptors comprising a GPC2-specific VH single domain antibody are also described. T cells expressing the GPC2-specific CARs potently killed GPC2-positive neuroblastoma cells in a dose-dependent manner.

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Laurel, MD, United States of America

Nan Li