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Engineered Persistence for Any CAR

NanoKar Therapeutics

NanoKar’s ITAM optimization platform addresses the persistence, toxicity, and solid tumor barriers limiting today’s CAR-T therapies. A single intracellular modification. No changes to targeting, co-stimulation, or manufacturing. One platform applicable across your entire portfolio.

100%
Survival Across 5 Re-Challenges (B-ALL)
26
Tunable ITAM Signaling Variants
Any CAR
T Cell, NK Cell, or Macrophage
Zero
Manufacturing Changes Required
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The Opportunity

Persistence Is a Defining Bottleneck in CAR-T

The global CAR-T market exceeded $8 billion in 2025, with persistence and solid tumor efficacy representing the primary barriers to market expansion. Every FDA-approved CAR-T therapy uses the same wild-type CD3ζ intracellular signaling domain. That one-size-fits-all design drives three problems limiting the entire field: limited durability, severe toxicity, and failure in solid tumors. NanoKar addresses all three at the intracellular level.

The Challenge
Our Solution

Limited Persistence

Short-lived CAR-T cells allow cancer to escape treatment. 30-60% of hematological malignancies relapse after current CAR-T therapies.

ITAM-Optimized Persistence

ITAM-optimized CAR-T cells generate long-lasting memory T cells with reduced exhaustion markers (PD-1, Tim-3, Lag-3). In a preclinical B-ALL model, a single treatment achieved 100% survival across five consecutive tumor re-challenges.

Severe Toxicity

Current therapies carry significant toxicity risk. 46% of patients exhibit features of severe CRS, with up to 9.1% of cases progressing to fatal outcomes.

Calibrated Signaling

26 ITAM signaling variants enable precise tuning of T cell activation. Signal intensity can be matched to clinical context, controlling the activation response at its source rather than through add-on safety mechanisms.

Solid Tumor Barrier

CAR-T efficacy in solid tumors remains limited, with only a 9-15% complete response rate across all solid tumor clinical trials.

Low-Antigen Sensitivity

ITAM optimization enhances CAR-T sensitivity to low antigen density, the defining challenge of solid tumors. Preclinical GD2 glioblastoma models demonstrate superior in vitro killing, and HER2 breast cancer solid tumor studies are in progress.

Science

A New Framework for CAR-T Engineering

NanoKar’s platform was developed in the laboratory of Dr. Matthew Bettini at the University of Utah Department of Pathology, with collaborators in pharmacology, biophysics, and cancer biology. The technology is exclusively licensed to NanoKar Therapeutics. Manuscript under peer review (2026). Preprint available upon request.

Discovery

CARs as Mechanosensors

Demonstrated for the first time that chimeric antigen receptors form catch bonds with antigen, functioning as mechanosensors analogous to T cell receptors. The lead construct, ζ-CCC, achieves peak bond lifetime at 22.2 pN of applied force. 26 unique signaling profiles with distinct force, bond lifetime, and activation characteristics.

Mechanism

Tunable Signal Strength

Phosphoproteomic analysis (14,000+ unique phosphopeptides) revealed that specific ITAM sequences alter downstream signaling cascades, cytoskeletal dynamics, and metabolic programming. Lower signal intensity correlates with enhanced memory formation.

Efficacy

In Vivo Results

The lead ζ-CCC construct demonstrated significantly improved tumor control in CD19+ hematological models, with 100% survival across five consecutive weekly tumor re-challenges in a B-ALL model. Sustained cytokine production at 29 days post-treatment.

Sensitivity

Low-Antigen Targeting

ζ-CCC CAR-T cells showed significantly improved cytotoxicity against low-antigen-expressing targets in vitro. GD2 glioblastoma models also demonstrate superior in vitro killing, with additional solid tumor studies underway.

Intellectual Property: Non-provisional patent application 19/198,917 filed, covering ITAM diversity optimization across any chimeric antigen receptor construct (T cell, NK cell, B cell, macrophage, and others) that utilizes CD3 zeta ITAMs.
Strategic Fit

A Platform That Enhances Existing Programs

NanoKar is a modular intracellular optimization layer, not a competing CAR-T product. The technology integrates into any CAR architecture without altering targeting domains, co-stimulatory elements, or manufacturing processes.

Standard CAR-TNext-Gen ApproachesNanoKar ITAM Optimization
LayerWild-type CD3ζ signalingExtracellular & structural modificationsIntracellular signaling domain
ExamplesAxi-cel, Tisa-cel, Liso-celArmored CARs, logic gates, allogeneic platforms26 tunable ITAM combinations
Toxicity ControlUncontrolled (100% grade 3+ SAEs in recent Phase 1*)Bolt-on kill switches, post-activationTuned at the activation signal source
PersistenceNone (native signaling)Add-on safety switches, co-stimulatory editsOptimized at the activation signal source
ManufacturingBaselineOften requires new vectors, processes, or cell sourcesZero changes. Encoded at the DNA construct level
CompatibilityAutologous T cells onlyPlatform-specific (often single cell type)Any CAR: T cell, NK cell, macrophage, TCR, and BCR constructs
RegulatoryEstablished IND pathwayOften requires new IND categoryFits within existing IND frameworks. Positioned for FDA Platform Technology Designation
*In vivo BCMA CAR-T Phase 1 trial, Nature Medicine, March 2026
Competitive Landscape

Orthogonal & Complementary

Other persistence approaches (armored CARs, checkpoint knockouts, epigenetic reprogramming, next-gen co-stim domains) modify the extracellular or structural layer. NanoKar operates at a distinct intracellular layer and can be combined with any of them without altering construct design or manufacturing.

Regulatory Pathway

FDA Platform Technology Designation

NanoKar’s platform is positioned to leverage the FDA’s Platform Technology Designation program. Approval of a first ITAM-optimized product could streamline the regulatory path for all subsequent programs built on the same platform.

Development

Pipeline

NanoKar is at the preclinical stage with IND-enabling studies planned.

TargetIndicationProgressStage
CD19B-Cell Malignancies (B-ALL, Lymphoma)
Preclinical Validation
HER2Breast Cancer (Solid Tumor)
Discovery
GD2Glioblastoma (Solid Tumor)
Discovery
Nectin4Bladder Cancer
Pending
EGFRvIIITriple Negative Breast Cancer
Pending
B7-H3Ovarian Cancer
Pending
Publications

Research

Peer Review

Selective CD3ζ ITAM Engineering of Chimeric Antigen Receptors Tunes Catch Bond Dynamics and Function

Echelibe H, Kolawole EM, Majumdar S, Lee W, Spainhower K, Liu B, Jensen P, Bettini M, Golkowski M, Evavold BD, Bettini ML. Manuscript under peer review (2026). Preprint available upon request.

Leadership

Our Team

Craig Mosman
Craig Mosman, J.D.
Chief Executive Officer
Leading NanoKar’s operations and IND-enabling program planning. Co-founded Seek Labs, where he led business development for nearly a decade. Former President of Kirkland Biotechnologies, investing in and commercializing early-stage biotech companies. J.D. with international business development experience across six continents.
Matt Bettini, Ph.D.
Matt Bettini, Ph.D.
Co-Founder & Chief Scientific Officer
Inventor of NanoKar’s ITAM optimization platform and named inventor on the company’s foundational patent. Senior author on the manuscript currently under peer review. Professor at the University of Utah Department of Pathology, with 15 years of expertise in immune tolerance, T cell engineering, and CAR-T mechanobiology. Ph.D. from Emory University with postdoctoral training at St. Jude Children’s Research Hospital.
Ross Eldridge
Ross Eldridge
Co-Founder & Board Member
Co-founded NanoKar to bring institutional-grade capital discipline and board governance to early-stage therapeutic development. Two decades in healthcare private credit and private equity, with prior board experience across portfolio companies. Built a $3.5B healthcare credit platform with zero realized credit losses. $35B+ in career transaction volume. Wharton alumnus.
Advisors

Scientific Advisory Board

Daniel Couriel, MD, MS, MBA
Scientific Advisor
Medical Director, Huntsman Cancer Institute Center for Cellular Therapy & Regenerative Medicine. Endowed Chair in Hematology at the University of Utah. Board member for ASTCT and FACT.
Alana Welm, Ph.D.
Scientific Advisor
Senior Director of Basic Science at Huntsman Cancer Institute. 20 years of experience with preclinical cancer therapeutics in mouse and patient-derived models.
Jens Lohr, MD, Ph.D.
Scientific Advisor
Director of the University of Utah Cellular Therapy and Regenerative Medicine Program. Director of Immunotherapies, Division of Hematology and Hematological Malignancies.
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Get in Touch

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Partner with NanoKar

Whether you are a potential strategic partner, co-development collaborator, or investor, we welcome the opportunity to discuss how NanoKar’s ITAM optimization platform can advance your cell therapy programs.

info@nanokartherapeutics.com
Salt Lake City, Utah