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IgG4 Hinge Containing Nanobody-based CARs Targeting GPC3 for Treating Liver Cancer

Scientists at the National Cancer Institute (NCI) developed a potent chimeric antigen receptor (CAR) targeting glypican-3 (GPC3). GPC3 is a cell surface proteoglycan preferentially expressed on Hepatocellular Carcinoma (HCC). The specific HN3 nanobody-IgG4H-CD28TM CAR included in this invention was much more potent both in in vitro cell models and in vivo mouse models. The NCI seeks licensing and/or co-development research collaborations for further development of the anti-GPC3 CAR to treat liver cancer.

T-cell Receptor Targeting Human Papillomavirus-16 E7 Oncoprotein

The National Cancer Institute (NCI) seeks research co-development partners and/or licensees for a T-cell receptor (TCR) that confers high-avidity recognition of the HPV-specific oncoprotein E7. The TCR may be used in an adoptive cell therapy approach utilizing genetically engineered lymphocytes to treat HPV-positive malignancies.

Bicistronic Chimeric Antigen Receptor (CAR) Constructs Targeting CD19 and CD20

Chimeric Antigen Receptors (CARs) are engineered proteins that can be used in a therapeutic capacity when expressed by an immune cell (e.g., a T cell). Specifically, CARs comprise a targeting domain (such as an antibody or binding fragment thereof) as well as domains that activate immune cells. By selecting a targeting domain that binds to a protein that is selectively expressed on a cancer cell, it is possible to target immune cells to the cancer cells. Upon binding to the target cell, the immune cells are activated, leading to the destruction of the cancer cell. This therapeutic approach holds great promise, as evidenced by the recent FDA-approval of CAR-T cell therapies, KYMRIAH and YESCARTA, both of which target CD19.

New T-Cell Immunotherapy that Targets Aggressive Epithelial Tumors

Researchers at the National Cancer Institute’s Experimental Transplantation and Immunology Branch (NCI ETIB) developed a T Cell receptor that specifically targets the Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1) 52-60 epitope that is highly expressed by several common and aggressive epithelial tumor types.

T-cell Receptors Targeting CD20-Positive Lymphomas and Leukemias

The National Cancer Institute (NCI) seeks licensees for a collection of T-cell receptors (TCRs) that specifically target the CD20 antigen expressed in B-lymphoid malignancies such as non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia, and acute lymphoblastic leukemia. The TCRs are being developed as therapeutics for the treatment of lymphomas and leukemias.

Anti-SLAMF7 Chimeric Antigen Receptors

Chimeric Antigen Receptor T cell (CAR-T) therapies that specifically target Signaling Lymphocyte Activation Molecule F7 (SLAMF7) are strong therapeutic candidates for patients with Multiple Myeloma (MM). SLAMF7 is highly expressed on the malignant plasma cells that constitute MM. The expression of SLAMF7 by MM cells and lack of expression on nonhematologic cells makes SLAMF7 an attractive therapeutic target for MM. Researchers at the National Cancer Institute (NCI) have invented anti- SLAMF7 CAR constructs that allow genetically-modified T cells to express both the anti-SLAMF7 antibody and a suicide gene that allows T cells to specifically recognize and kill SLAMF7-expressing cells as well as allow for on-demand and reliable elimination of anti-SLAMF7 CAR T cells. NCI seeks licensing and/or co-development partners for this invention.

High Affinity Monoclonal Antibodies Targeting Glypican-2 for Treating Childhood Cancers

Cancer therapies that specifically target Glypican 2 (GPC2) are strong therapeutic candidates for pediatric patients with neuroblastoma and other GPC2 expressing cancers. The inventors at the National Cancer Institute (NCI) have developed and isolated two new antibodies that target GPC2 (CT3 and CT5) that are available for licensing and co-development.

High Affinity Nanobodies Targeting B7-H3 (CD276) for Treating Solid Tumors

Researchers at the National Cancer Institute (NCI) have isolated a panel of anti-CD276 (also called B7-H3) single domain antibodies (also known as nanobodies). These antibodies have a high affinity for CD276-positive tumor cells and have great potential for diagnostic and therapeutic technologies against solid tumors. The NCI seeks licensing and/or co-development research collaborations for CD276-targeting camel nanobodies.

Inhibition of T Cell Differentiation and Senescence by Overexpression of Transcription Factor c-Myb

Researchers at the National Cancer Institute (NCI) have developed a method by which memory T cells can be generated from other T cell populations using overexpression of the transcription factor c-Myb. Importantly, these reprogrammed memory T cells show increased proliferative and survival capacity. This strategy could also potentially generate anti-tumor T cells with improved viability and therapeutic efficacy for adoptive ACT. Researchers at the NCI seek licensing and/or co-development research collaborations for this invention.

T Cell Receptors Targeting KRAS Mutants for Cancer Immunotherapy/Adoptive Cell Therapy

Researchers at the National Institutes of Health identified a collection of TCRs that exclusively recognize the common hotspot driver mutations in KRAS antigen, expressed by a variety of epithelial cancers, including pancreatic, colorectal and lung cancer. The mutated KRAS variants are recognized by the TCRs in the context of specific Class I/Class II HLA alleles. These TCRs can be used for a variety of experimental therapeutic, diagnostic and research applications.

Methods for Producing Stem Cell-Like Memory T Cells for Use in T Cell-Based Immunotherapies

Researchers at the National Cancer Institute (NCI) seek research & co-development and/or licensees for a novel, ex vivo method by which stem cell-like memory T cells (Tscm) can be generated by stimulating naïve T cells in the presence of inhibitors of GSK-3beta, which are capable of activating the Wnt pathway. These Tscm cells, generated using GSK-3beta inhibitors, display enhanced survival and proliferation upon transfer, have multipotent capacity to generate all memory and effector T cell subsets, and show increased anti-tumor activity in a humanized mouse tumor model.

In vitro Generation of an Autologous Thymic Organoid from Human Pluripotent Stem Cells

The thymus is the only organ capable of producing conventional, mature T cells; a crucial part of the adaptive immune system. However, its efficiency and function are progressively reduced as we age, leading to a compromised immune system in the elderly. Moreover, production of T cells with specific receptors is an important concern for cancer immunotherapy. Current in vitro methods produce immature T cells that are not useful for therapy. Researchers at the National Cancer Institute (NCI) have generated an autologous thymic organoid from human pluripotent stem cells to address this problem. The organoid can be used to develop clinical applications such as production of autologous T and natural killer T (NKT) cells and reconstitution of the adaptive immune system. NCI is seeking licensees for the thymic organoid and the method of its generation to be used in a variety of clinical applications.

Efficient Methods to Prepare Hematopoietic Progenitor Cells in vitro for Therapeutic Use

Multi-potential hematopoietic progenitor cells (HPC) can differentiate into any class of blood cells, and are highly useful in regenerative medicine, immunology, and cancer immunotherapy. Current methods to generate HPCs are limited either due to the use of animal products, or the high cost and low efficiency of animal product free systems. Researchers at the National Cancer Institute (NCI) have developed a protocol to prepare HPCs from human induced pluripotent stem cells (hiPSC), using human mesenchymal stem cells (hMSC) in a three-dimensional (3D) co-culture condition. Thus, they are able to generate HPCs in a fully human, autologous system, which can be used to further generate immune cells for therapy. This protocol is adaptable to mass production by bioreactors. NCI seeks licensees for these methods of generating HPCs in a 3D co-culture with hMSCs to be used in a variety of applications such as treatment of blood disorders, regenerative medicine, and antibody production.

Cancer-reactive T cells from Peripheral Blood

T-cells capable of reacting to mutations in cancer patients have potential use as therapeutics. Identifying and isolating these cells from patients is a crucial step in developing these treatments. Researchers at the National Cancer Institute (NCI) have developed a novel method of isolating mutation-reactive T-cells from a patient’s peripheral blood lymphocytes (PBL). The NCI, Surgery Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this method of isolating mutation-reactive T-cells from peripheral blood.

Methods of Producing Thymic Emigrants from Induced Pluripotent Stem Cells

Pluripotent stem cells are a promising source of T cells for a variety of clinical applications. However, current in vitro methods of T cell differentiation result in the generation of cells with aberrant phenotypes. Researchers at the National Cancer Institute (NCI) have now developed methodology for generating induced pluripotent stem cell thymic emigrants (iTE). Antigen-specific CD8αβ+ iTEs exhibited functional properties in vitro that were almost indistinguishable from natural naïve CD8αβ+ T cells, including vigorous expansion and robust anti-tumor activity. iTEs recapitulated many of the transcriptional programs of naïve T cells in vivo and revealed a striking capacity for engraftment, memory formation, and efficient tumor destruction. The NCI seeks licensing and/or co-development research collaborations for this invention.

Novel Murine T-Cell Receptors for Treating Metastatic Thyroid Cancer

Metastatic thyroid cancer can be resistant to current treatment options such as radioactive iodine therapy. Targeting thyroglobulin, a thyroid-specific antigen, as part of an adoptive cell therapy approach will allow for new therapeutic possibilities. Researchers at the National Cancer Institute (NCI) seek licensing and/or co-development research collaborations for novel T-cell receptors for the treatment of metastatic thyroid cancer.

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