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 preclinical signs of efficacy 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 preclinical signs of efficacy 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 xenograft B-ALL model (n=8), a single treatment achieved 100% survival across five consecutive tumor re-challenges.
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.
26 ITAM 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.
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 models demonstrate superior in vitro killing, and HER2 breast cancer solid tumor studies are in progress.
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). Preprint available upon request.
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 demonstrated significantly improved tumor control in CD19+ hematological models, with 100% survival (n=8) 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. GD2 glioblastoma models also demonstrated superior in vitro killing, with additional solid tumor studies underway.
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 Control | Uncontrolled (100% grade 3+ SAEs in recent Phase 1*) | Bolt-on kill switches, post-activation | Tuned at the activation signal source |
| Persistence | None (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 |
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. This extends to delivery. Because the optimization is encoded in the genetic construct itself, it is independent of how the CAR is generated, applying equally to ex vivo (autologous and allogeneic) and emerging in vivo approaches.
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.
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 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 Therapeutics has secured an exclusive global license from the University of Utah Technology Licensing Office for a novel CAR-T cell engineering platform developed by Matthew Bettini, Ph.D. The licensed ITAM optimization technology is designed to tune intracellular CAR signaling to improve persistence, reduce toxicity, and expand efficacy in solid tumors.
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.