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@pci.upenn.edu.  

Performance Enhancement Category	Technology	Keywords	Reference
Phenotype, proliferation and exhaustion	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, Prostate cancer	EP 3286211
Phenotype, proliferation and exhaustion	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	CAR-T expansion, Tet1, Tet2, Tet3	WO 2017049166
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
Phenotype, proliferation and exhaustion	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
Enhanced cytokine activity	CAR T therapy in combination with IL-15R and IL15 Methods for increasing persistance and anti-cancer activity of T-cells by co-transduction of IL15Rα-T2A-IL15 and chimeric antigen receptors.	IL15, IL15R	WO 2019160956
Manufacturing	A method to harness patient’s antibodies and transform them to highly potent, T-cell redirecting antibodies for treatment of cancerous tumors T cell redirecting antibodies Docket #: 18-8590	Bispecific T cell-redirecting autoantibodies	Inquire
Phenotype, proliferation and exhaustion	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	CAR-T and NK synergy,  Sialidase, Neuraminidase, Solid tumors	WO 2020236964
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	Metabolic enzyme expression, Nutrient-poor environment	WO 202004166
Phenotype, proliferation and exhaustion	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
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 phenotype, Proliferation, Prostate cancer	WO 2023/086882 A1
Phenotype, proliferation and exhaustion	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	Donor cell expansion, IL2 receptor beta	WO 2022/192346
Phenotype, proliferation and exhaustion	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	Exhaustion, CRISPR-KO, Sox4, ID3	WO 2022/192249
Phenotype, proliferation and exhaustion	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	Inflammatory function, Regnase-1, Roquin-1	WO2023070080
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 inhibition	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
Manufacturing	Methods to PEGylate CAR-T cells to block the interactions with monocytes and macrophages to reduce cytokine release syndrome and neurotoxicity In situ PEGylation of CAR T cell therapeutics to alleviate cytokine release syndrome and neurotoxicity. Docket #: 22-10066	PEGylation, Cytokine release syndrome	Inquire
Manufacturing	Methods for optimizing T cell immunotherapeutic effector and memory function Methods to allows the distinction of proximal and distal first division daughter CAR cells, with favorable implications for memory phenotype. Docket #: 22-10074	Memory phenotype, asymmetric T cell division, LIPSTIC	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
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
Phenotype, proliferation and exhaustion	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	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	Host immunosuppression, HVEM, BTLA	Inquire
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
Metabolism	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	Cytolytic activity, Diacylglyceral kinase	WO 2014039513
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	Tumor-infiltrating lymphocyte, CD137	Technology Summary

For inquiries and further exploration of technologies available from Penn, please reach out to CAR-T@pci.upenn.edu. Download the most updated version of the table here. Last updated 12/14/23.