NanoKar is an optimization layer for any CAR-T program, not a competing CAR-T. We tune the CD3ζ domain that every approved CAR-T shares, whatever the cancer, extending persistence and reducing toxicity. CAR-T has stalled in solid tumors. Our data points the other way.
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.
Calibrated signaling widens the dose 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.
One inherited CD3ζ design drives the three problems limiting the entire field.
Toxicity caps the dose, and dose is what solid tumors demand.
Calibration runs in both directions. The right signal, not the maximum: persistence up, toxicity down.
The domain stayed fixed because the three ITAMs were treated as one setting that fires all at once, unchanged since the first CAR in the 1990s. The work behind NanoKar showed that CARs behave as mechanosensors, and that ITAM sequence sets which switches fire and how hard, which turns a fixed component into a design parameter.
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, with 100% survival across five consecutive weekly tumor re-challenges in a CD19 xenograft B-ALL model, reduced exhaustion markers (PD-1, Tim-3, Lag-3), and sustained cytokine production at 29 days post-treatment.
The leading ζ-ITAM-optimized CAR-T cells demonstrated significantly improved cytotoxicity against low-antigen-expressing targets in vitro.
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 | Next Up | |
| EGFRvIII | Glioblastoma (Solid Tumor) | Next Up | |
| B7-H3 | Ovarian Cancer | Next Up | |
| BCMA | Multiple Myeloma | Next Up |
Where ITAM optimization sits relative to the approved products and the next-generation approaches.
| 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 and limited persistence, both set by native signaling | Toxicity managed downstream with 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, any target: T cell, NK cell, macrophage and more, in blood cancers and solid tumors |
| 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 | A new construct, so it belongs in a program before IND, not a retrofit of an approved product. Positioned for FDA Platform Technology Designation, which could streamline the path for later programs on the same platform |
Nearly every next-generation approach modifies the targeting, structural, or co-stimulatory layer. NanoKar works on the fourth, so it combines with these approaches rather than replacing them. Your program keeps its targeting, its co-stimulation, and its manufacturing.
Every delivery platform acquired to date runs the same unoptimized signaling engine. 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, gene-edited, or allogeneic designs.
For an approved or clinical CAR-T franchise, ITAM optimization adds a persistence and toxicity differentiator at the construct level, with no change to targeting or manufacturing.
Autoimmune CAR-T needs a controlled immune reset, not maximum activation. The 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 xenograft dataset, phosphoproteomics, and construct-level detail are available under NDA. Partners can evaluate lead constructs in their own models under MTA.
NanoKar’s advisors are affiliated with Huntsman Cancer Institute and the University of Utah.
NanoKar Therapeutics has joined Altitude Lab, the Recursion-founded life science accelerator in Salt Lake City, as a resident company. The move adds specialized laboratory resources and direct connectivity to global biopharma executives, strategic acquirers, and investors as NanoKar scales its preclinical translational studies and business development.
Read the full releaseNanoKar 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 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.