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, with early preclinical signals in solid tumors.
Every FDA-approved CAR-T therapy uses the same intracellular CD3ζ signaling domain sequence. This one-size-fits-all design drives three problems limiting the entire field: limited persistence, severe toxicity, and failure in solid tumors. NanoKar addresses persistence and toxicity at the intracellular level, with early preclinical signals in solid tumors.
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 46% 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 only a 9-15% complete response rate across all solid tumor clinical trials.
ITAM optimization enhances CAR-T sensitivity to low antigen density, the defining challenge of solid tumors. Preclinical GD2 glioblastoma and HER2 PDX breast cancer studies are underway.
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 carries the same three CD3ζ ITAMs in the same configuration. NanoKar engineers that configuration, leaving the targeting domain, co-stimulatory element, and manufacturing process untouched.
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 Burden | Severe CRS up to 46% in some approved-product trials (ELIANA) | Up to 100% grade 3+ SAEs in a recent Phase 1* | Tuned at the activation signal source |
| Persistence | Limited (native signaling) | Add-on safety switches, co-stimulatory edits | Optimized at the activation signal source |
| 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’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. Three 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.
Your delivery stack still carries a CD3ζ construct that no one has optimized. ITAM tuning improves what the cell does once engineered, independent of how it is delivered.
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.
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) | Discovery | |
| GD2 | Glioblastoma (Solid Tumor) | Discovery | |
| Nectin4 | Bladder Cancer | Pending | |
| EGFRvIII | Triple Negative Breast Cancer | 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.