CAR-T Enhancing Technologies
As the home of the first FDA-approved chimeric antigen receptor (CAR) T cell therapy, the University of Pennsylvania boasts an enduring legacy as a pioneer in CAR technology. The Penn Center for Innovation helps to translate the discoveries and ideas created in labs at Penn into new products and businesses for societal benefit. Here, we present our portfolio of CAR enhancement technologies—a compilation of intellectual properties with the overarching objective of advancing CAR T-cell therapy efficacy. This diverse array of CAR T-cell adjunctive technologies encompasses methods to augment cytokine activity, improve manufacturing, reduce exhaustion, and overall, enhance CAR T-cell therapies.
We invite forward-thinking companies to explore the immense potential within our portfolio of CAR technologies, with the opportunity to license these innovations for commercialization. For inquiries and further exploration of technologies available from Penn, please reach out to CAR-T@pobox.upenn.edu.
Performance Enhancement Category | Technology | Keywords | Reference |
Enhanced cytokine activity | CAR T therapy in combination with IL-15R and IL15 Methods for increasing persistence and anti-cancer activity of T-cells by co-transduction of IL15Rα-T2A-IL15 and chimeric antigen receptors. Docket #: 18-8579 | IL15, IL15R | WO 2019160956 |
Enhanced cytokine activity | Treatment of cancer by inhibition of Blimp-1 (PRDM1) in the setting of gene-modified T cell therapy Methods to develop PRDM1 and NR4A3 deficient CAR T-cells which demonstrate heightened proliferation, sustained central memory T-cell phenotype, elevated effector cytokine secretion, and tumor treatment outcomes. Docket #: 20-9204 | Blimp-1, PRDM1, Central memory T cell phenotype, Proliferation, Prostate Cancer, Prostate-specific membrane antigen | WO 2023/086882 A1 |
Enhanced cytokine activity | Chimeric cytokine receptors for enabling adoptive T cell therapy of solid tumors via IL-9 signaling Development of a CAR that comprises an intracellular signaling domain of IL9 receptor alpha (IL9Ra) combined with IL9, IL13, IL2, or IL18 cytokine expression and Cullin 5 suppression. Docket #: 21-9767 | IL9, IL13, IL2, IL18, Cul5 | WO 2023/044456 |
Enhanced cytokine activity | Orthogonal cytokine enhanced CAR T cells generated through gene editing Methods to modulate IL-2 and IL-15 responsiveness through expression of orthogonal IL2RB establishing a proof-of-concept for using orthogonal cytokines with ACT. Docket #: 22-10028 | Orthogonal cytokines, IL2, IL15 | Inquire |
Enhanced cytokine activity | Potentiating adoptive cell therapy using synthetic IL-9 receptors CAR that comprises an intracellular signaling domain of an IL9 receptor alpha (IL9Ra). Docket #: 22-9826 | IL9, IL9R | WO 2023044453 |
Enhanced cytokine activity | Immunocytokines for specific augmentation of CAR T cells Methods to selectively express immunostimulatory cytokines on CAR T-cells for localized cytokine delivery. Docket #: 23-10290 | Cytokine delivery | Inquire |
Enhanced cytokine activity | Inhibition of diacyclglyceral kinase (DGK) to augment adoptive T cell transfer Methods to improve cytolytic activity of T-cells by inhibiting diacylglyceral kinase. Docket #: Y6336 | DGK, Diacylglyceral kinase | WO 2014039513 |
Manufacturing | Single vector systems for simultaneous but independent constitutive and antigen-induced transgene expression A single lentiviral vector system that integrates constitutive immune receptor expression and autonomous inducible expression based on antigen recognition and microenvironment to improve the targeting and specificity of immunotherapy. Docket #: 17-8348 | Lentiviral, Constitutive immune receptor expression | Technology Summary |
Manufacturing | Methods for optimizing T cell immunotherapeutic effector and memory function Methods that allow the distinction of proximal and distal first division daughter CAR cells, with favorable implications for memory phenotype. Docket #: 22-10074 | Asymmetric T cell division, Memory T cell phenotype | Inquire |
Manufacturing | Decoy HLA-E SCT for allogeneic donor cells A method of CAR T-cell modification that genetically removes surface proteins to lower the risk of immune allo-recognition and adds peptides to prevent self-attack in graft vs host disease (GVHD). Docket #: 22-9914 | Universal donor, Allogenic therapy, NK cytotoxicity, Graft Versus Host Disease | Inquire |
Manufacturing | CD137 enrichment for efficient TIL selection A platform for the isolation and expansion of CD137-positive tumor-infiltrating lymphocytes to use in adoptive immunotherapy and translational studies. Docket #: Z6725 | CD137, Tumor-infiltrating lymphocyte | Technology Summary |
Manufacturing | In situ PEGylation of CAR T cell therapeutics to alleviate cytokine release syndrome and neurotoxicity Methods to PEGylate CAR-T cells to block the interactions with monocytes and macrophages to reduce cytokine release syndrome and neurotoxicity. Docket #: 22-10066 | PEGylation, cytokine release syndrome | Inquire |
Manufacturing | Bispecific T cell-redirecting autoantibodies A method to harness patient’s antibodies and transform them to highly potent, T-cell redirecting antibodies for treatment of cancerous tumors. Docket #: 18-8590 | T cell redirecting antibodies | Inquire |
Metabolism | Enhancing CAR T therapy with metabolic enzyme expression Methods to enable CAR immune cells to overcome nutrient-limited tumor environments for competitive advantage over cancer cells. Docket #: 20-9098 | Asparagine, Aspartate transcarboxylase, Aspartate tRNA synthetase, Alanine/aspartate/or asparagine transporter(s) | WO 202004166 |
Phenotype, proliferation and exhaustion inhibition | Improvement in efficacy of adoptive transfer of T cells by the genetic addition of a small peptide encoding a protein kinase A regulatory subunit I anchoring disruptor (RIAD) Enhanced tumoricidal efficiency in adoptive T-cells engineered to co-express RIAD-RISR peptide along with either CAR or engineered TCR. Docket #: 15-7306 | RIAD-RISR, Solid tumors | EP 3286211 |
Phenotype, proliferation and exhaustion inhibition | Modulation of methylcytosine dioxygenases for improving the therapeutic efficacy of gene-modified antigen-specific T cells Rapid massive expansion of clonal CAR T cell population and increased functional activity of T-cells via the disruption of methylcytosine dioxygenase genes (e.g., Tet1, Tet2, Tet3). Docket #: 16-7609 | Tet1, Tet2, Tet3 | WO 2017049166 |
Phenotype, proliferation and exhaustion inhibition | Combination of CART and SMAC mimetics for cancer treatment A small molecule SMAC-mimetic used in conjunction with CAR T-cell therapy increases efficacy of cancer treatment. Docket #: 18-8446 | SMAC, SMAC-mimetic | WO 2019165215 |
Phenotype, proliferation and exhaustion inhibition | Engineered expression of cell surface and secreted sialidase by CAR T cells for increased efficacy in solid tumors Methods for human sialidase and neuraminidase-expression to promote synergistic cytotoxicity effects between CAR T- and NK cells. Docket #: 19-8906 | NK cells, Sialidase, Neuraminidase | WO 2020236964 |
Phenotype, proliferation and exhaustion inhibition | Enhancing CAR T cell efficacy using Neuraminidase as well as Galactose Oxidase Methods to significantly enhance the killing of solid tumor cells by CAR T-cell therapy through inducible expression of neuraminidase and galactose oxidase. Docket #: 20-9103 | Neuraminidase, Galactose Oxidase | WO 2023/015300 |
Phenotype, proliferation and exhaustion inhibition | Selective stimulation of T cells in solid tumors using oncolytic viral delivery of orthogonal IL-2 Selective stimulation and expansion of CAR T-cells through the expression of an orthogonal IL2 receptor beta allowing specific activation of tumor-targeting cells without triggering endogenous IL2. Docket #: 20-9235 | IL2, Orthogonal IL2 receptor beta | WO 2022/192346 |
Phenotype, proliferation and exhaustion inhibition | CRISPR mediated knock out of SOX4 and ID3 delays T cell dysregulation induced by chronic antigen exposure Downregulation of endogenous SOX and/or ID3 to forfend T-cell exhaustion. Docket #: 21-9509 | Sox4, ID3, T cell exhaustion, Immuno-oncology | WO 2022/192249 |
Phenotype, proliferation and exhaustion inhibition | Knockout of Regnase-1 and Roquin-1 alone or together to enhance CAR T cell activity Knockout of Regnase-1 and Roquin-1 to potentiate greater inflammatory CAR T-cell function and persistence against cancer. Docket #: 21-9707 | Regnase-1 (Reg-1), Roquin-1 (Roq-1) | WO2023070080 |
Phenotype, proliferation and exhaustion inhibition | Compositions and methods for enhancing the anti-tumor activity of CAR T cells by co-expression of Ch25h Enhancing anti-tumor activity, inhibiting trogocytosis, decreasing T cell exhaustion, and increasing viability of CAR T cells by co-expression with cholesterol 25-hydroxylase (CH25H) in a single construct for treatment of solid tumor and hematological cancers. Docket #: 22-9930 | Cholesterol 25-hydroxylase (CH25H), Trogocytosis | Technology Summary |
Phenotype, proliferation and exhaustion inhibition | HVEM and BTLA modulation to enhance CART immunotherapy Method for enhancing CAR-T immunotherapy via protein mutation to disrupt host immunosuppression and increase CAR effectiveness. Docket #: 22-9982 | HVEM, BTLA, Immunosuppression | Inquire |
Download the most updated version of the table here. Last updated 11/20/23.