NanoKar is an optimization layer for existing CAR-T therapies, not a competing CAR-T. Our ITAM tuning platform addresses the persistence and toxicity barriers limiting the field today. Solid tumors are the open field in cell therapy, and calibrated signaling is how cell therapy gets there.
A two-minute explainer: what a CAR is, what an ITAM does, and why NanoKar is the optimization layer for any CAR.
Every approved CAR-T carries the same CD3ζ signaling domain. One fixed sequence, never engineered. NanoKar engineers it. 26 tunable ITAM variants let activation be calibrated rather than fixed, shifting T cells toward memory instead of exhaustion. Nothing else about the construct changes.
Toxicity caps the dose. Dose is what solid tumors demand. Calibrated signaling widens the window at the source, and it travels with any CAR, any cell type, any delivery, with no change to targeting, co-stimulation, manufacturing, or regulatory path.
Every FDA-approved CAR-T therapy uses the same intracellular CD3ζ signaling domain sequence. That single design drives the three problems limiting the entire field: limited persistence, severe toxicity, and failure in solid tumors. Calibration runs in both directions: the variant library spans weaker and stronger signaling than the native domain, so potency can be raised or lowered depending on the program.
Short-lived CAR-T cells allow cancer to escape treatment. 30-60% of hematological malignancies relapse after current CAR-T therapies.
ITAM-optimized CAR-T cells generate long-lasting memory T cells with reduced exhaustion markers (PD-1, Tim-3, Lag-3). In a CD19 model, ITAM optimization produced durable tumor control across consecutive re-challenges versus the same CAR carrying the standard CD3ζ domain, in the same model. Data available under NDA.
Current therapies carry significant toxicity risk. Severe CRS rates reach 48% in some approved-product trials (ELIANA), and CRS remains a boxed warning across the class.
26 ITAM variants enable precise tuning of T cell activation. Signal intensity can be matched to clinical context, controlling activation at its source, a mechanism-based route to lower CRS risk that add-on kill switches cannot provide.
CAR-T efficacy in solid tumors remains limited, with a pooled objective response rate of approximately 9% across solid tumor clinical trials.
In vitro, ITAM-optimized CAR-T cells showed significantly improved cytotoxicity against low-antigen-expressing targets. Low antigen density is a defining barrier in solid tumors. Preclinical GD2 glioblastoma and HER2 PDX breast cancer programs are advancing. Data available under NDA.
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 revision (2026). Available to partners under NDA.
Every approved CAR-T uses the same CD3ζ ITAM configuration. NanoKar engineers that configuration across 26 variants, holding the targeting domain, co-stimulatory element, and manufacturing process constant, and shifting the activation signal toward memory formation rather than exhaustion.
Data generated with ex vivo engineered CAR-T, the format every approved product uses.
Demonstrated for the first time that chimeric antigen receptors form catch bonds with antigen, functioning as mechanosensors analogous to T cell receptors. 26 unique predicted signaling profiles with distinct force, bond lifetime, and activation characteristics.
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.
The lead ζ-ITAM construct demonstrates significantly improved tumor control versus the same CAR carrying the standard CD3ζ domain in CD19+ hematological models, with 100% survival across five consecutive weekly tumor re-challenges in a CD19 xenograft B-ALL model. Sustained cytokine production was observed at 29 days post-treatment.
The leading ζ-ITAM-optimized CAR-T cells demonstrated significantly improved cytotoxicity against low-antigen-expressing targets in vitro.
The technology integrates into any CAR architecture without altering targeting domains, co-stimulatory elements, or manufacturing processes.
| Standard CAR‑T | Next-Gen Approaches | NanoKar ITAM Optimization | |
|---|---|---|---|
| Layer | Endogenous CD3ζ signaling | Extracellular & structural modifications | Intracellular signaling domain |
| Examples | Axi-cel, Tisa-cel, Liso-cel | Armored CARs, logic gates, allogeneic platforms | 26 tunable ITAM combinations |
| Toxicity and Persistence | Severe CRS up to 48% in some approved-product trials (ELIANA); persistence limited by native signaling | Up to 100% grade 3+ SAEs in a recent Phase 1; add-on safety switches and co-stimulatory edits | Both tuned at the activation signal source, not managed downstream |
| Manufacturing | Baseline | Often requires new vectors, processes, or cell sources | Compatible with existing workflows. Encoded at the DNA construct level |
| Compatibility | Autologous T cells only | Platform-specific (often single cell type) | Any CAR Construct: T cell, NK cell, Macrophage, TCR, BCR and more |
| Delivery | Ex vivo viral transduction | Platform-specific delivery vehicles | Delivery-agnostic. Encoded in the construct, portable across ex vivo and in vivo |
| Regulatory | Established IND pathway | Often requires new IND category | Fits within existing IND frameworks. Positioned for FDA Platform Technology Designation |
Nearly every next-generation approach modifies the targeting, structural, or co-stimulatory layer. The intracellular signaling layer has gone unchanged since the first approval. NanoKar works on that fourth layer, so it combines with these approaches rather than replacing them.
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.
ITAM optimization creates value differently depending on the program it enters. Four of the most direct fits:
For an approved or clinical CAR-T franchise, ITAM optimization adds a persistence and toxicity differentiator at the construct level, with no change to your targeting domain or manufacturing.
Persistence and low-antigen sensitivity are the recurring failure points. ITAM optimization targets both at the signal source and combines with armored, logic-gated, or gene-edited designs.
Your delivery stack still carries a CD3ζ construct no one has optimized. ITAM tuning improves what the cell does once engineered, independent of how it is delivered, and every delivery platform acquired to date carries an unoptimized construct.
Autoimmune CAR-T needs a controlled immune reset, not maximum activation, in patients who are not facing a terminal diagnosis. Our 26-variant library spans attenuated as well as enhanced signaling, which makes calibrated potency testable. We have not run autoimmune models. Our data is autologous oncology preclinical.
Full in vivo dataset, phosphoproteomics, and construct-level detail are available under NDA. Partners can evaluate lead constructs in their own models under MTA.
NanoKar is at the preclinical stage with IND-enabling studies planned.
| Target | Indication | Progress | Stage |
|---|---|---|---|
| CD19 | B-Cell Malignancies (B-ALL, Lymphoma) | Preclinical Validation | |
| HER2 | Breast Cancer (Solid Tumor) | Preclinical Validation | |
| GD2 | Glioblastoma (Solid Tumor) | Preclinical Validation | |
| Nectin4 | Bladder Cancer | Pending | |
| EGFRvIII | Glioblastoma (Solid Tumor) | Pending | |
| B7-H3 | Ovarian Cancer | Pending | |
| BCMA | Multiple Myeloma | Pending |



NanoKar’s advisors are affiliated with Huntsman Cancer Institute and the University of Utah.
NanoKar Therapeutics has been accepted into the Innosphere Ventures accelerator program in Fort Collins, Colorado. The program provides mentorship, investor access, and business development support as NanoKar advances its ITAM optimization platform for CAR-T cell therapy toward strategic partnerships.
Read the full releaseNanoKar Therapeutics has been awarded funding from the University of Utah Launchpad Seed Fund to advance its ITAM optimization platform for CAR-T cell therapy. The capital will support translational validation data, including CAR-T persistence and activity in solid tumor models, and help prepare the platform for evaluation by potential development partners.
Read the full releaseNanoKar Therapeutics has formally appointed Craig Mosman, J.D., as Chief Executive Officer. Mosman will lead the company’s partnership strategy and translational data priorities as it advances the ITAM optimization platform toward partner-ready commercialization.
Read the full releaseNanoKar is advancing discussions with strategic partners across the cell therapy landscape. If our platform aligns with your programs or investment focus, we’d welcome a conversation.
This website may contain forward-looking statements regarding NanoKar Therapeutics, Inc., including statements about the company’s research and development programs, the potential of its ITAM optimization platform, anticipated preclinical and clinical milestones, intellectual property, and plans for partnerships, financing, and commercialization. These statements are based on current expectations and assumptions and are subject to risks and uncertainties, including but not limited to risks associated with preclinical and clinical research, the timing and outcome of regulatory submissions and approvals, the success of clinical trials, manufacturing and supply, intellectual property protection and freedom to operate, competitive products and technologies, and the availability of financing on acceptable terms. Actual results may differ materially from those expressed or implied. NanoKar Therapeutics undertakes no obligation to update any forward-looking statement except as required by law. Nothing on this website constitutes an offer to sell or a solicitation of an offer to buy any securities, and no securities of NanoKar Therapeutics may be offered or sold in any jurisdiction in which such offer or sale would be unlawful.