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  

Performance Enhancement CategoryTechnologyKeywordsReference
Phenotype, proliferation and exhaustionImprovement 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 exhaustionModulation 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 exhaustionCombination 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-mimeticWO 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, IL15RWO 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 autoantibodiesInquire
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
MetabolismEnhancing 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 cancerWO 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 betaWO 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, ID3WO 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

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

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
Enhanced cytokine activityPotentiating 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, IL9RWO 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

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

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 

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

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 Download the most updated version of the table here. Last updated 12/14/23.

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