# CAR-NK & CAR-macrophage

Source: https://onco.cc/technologies/car-nk-macrophage/  
OnCo record `car-nk-macrophage` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Putting the cancer-seeking receptor on natural killer cells or macrophages instead of T cells, which could be safer and off-the-shelf.

## Summary

CAR-NK and CAR-macrophage therapies put a chimeric antigen receptor on innate effector cells instead of T cells; NK cells lack graft-versus-host risk, enabling allogeneic, off-the-shelf use with low cytokine release syndrome and neurotoxicity. Cord-blood or iPSC-derived CAR-NK (Nkarta, Fate, Takeda/MD Anderson) show low CRS and allogeneic feasibility, but efficacy durability is the question because persistence is short. CAR-macrophages (Carisma CT-0508, HER2) aim at solid tumour infiltration and phagocytosis, with early and modest results. Manufacturing scale is a further hurdle. The simple version is that these therapies use other immune cells as the cancer-seeking vehicle, promising safety and availability but not yet matching the durable responses of CAR-T.

## Fields

- Kind: Technology
- Status: phase-1
- Last checked: 2026-09-04
- Also known as: CAR-NK; CAR-NK cells; CAR-macrophage
- Tags: frontier
- Principle: Innate effector cells engineered with a CAR; NK cells lack GVHD risk enabling allogeneic use.
- Strengths: Off-the-shelf potential; Low CRS/ICANS
- Limitations: Short persistence; Manufacturing scale

## Sources

- Liu et al., CAR-transduced natural killer cells in CD19-positive lymphoid tumours (NEJM 2020): https://doi.org/10.1056/NEJMoa1910607
- Klichinsky et al., Human chimeric antigen receptor macrophages for cancer immunotherapy (Nature Biotechnology 2020): https://doi.org/10.1038/s41587-020-0462-y

## Connected records

- technologies: [Allogeneic (off-the-shelf) cell therapy](https://onco.cc/technologies/allogeneic-cell-therapy/), [Allogeneic cell banks: one donor, hundreds of doses](https://onco.cc/technologies/allogeneic-cell-banks/), [Allogeneic donor and iPSC master cell banks](https://onco.cc/technologies/allogeneic-cell-banking/), [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [Cell-therapy release and potency testing](https://onco.cc/technologies/cell-therapy-release-testing/), [NK cell therapy and CAR-NK](https://onco.cc/technologies/nk-cell-therapy/), [Trained innate immunity](https://onco.cc/technologies/trained-innate-immunity/), [Viral vector manufacturing (lentiviral, retroviral, AAV)](https://onco.cc/technologies/viral-vector-manufacturing/)
- fronts: [Cell Therapy](https://onco.cc/fronts/cell-therapy/)
- companies: [Fate Therapeutics](https://onco.cc/companies/fate-therapeutics/), [Indapta Therapeutics](https://onco.cc/companies/indapta-therapeutics/), [Nkarta](https://onco.cc/companies/nkarta/), [ONK Therapeutics](https://onco.cc/companies/onk-therapeutics/)
- key papers: [Human chimeric antigen receptor macrophages for cancer immunotherapy](https://onco.cc/key-papers/paper-klichinsky-nat-biotechnol/), [Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors](https://onco.cc/key-papers/paper-liu-n-engl-j-med/)
- institutions: [IRCCS Humanitas Research Hospital](https://onco.cc/institutions/humanitas/), [Kyoto University Hospital](https://onco.cc/institutions/kyoto-university-hospital/), [Masonic Cancer Center, University of Minnesota](https://onco.cc/institutions/minnesota-masonic/), [MD Anderson Cancer Center](https://onco.cc/institutions/md-anderson/), [QIMR Berghofer Medical Research Institute](https://onco.cc/institutions/qimr-berghofer/)
- roadmaps: [Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR](https://onco.cc/roadmaps/cell-therapy-roadmap/)
- people: [Hans-Gustaf Ljunggren](https://onco.cc/people/hans-gustaf-ljunggren/), [Katayoun Rezvani](https://onco.cc/people/katy-rezvani/), [Michael A. Caligiuri](https://onco.cc/people/michael-caligiuri/), [Rolf Kiessling](https://onco.cc/people/rolf-kiessling/)
- bottlenecks: [Manufacturing cost and time for living and radioactive medicines](https://onco.cc/bottlenecks/b-manufacturing-cell-therapy/)
- ideas: [Bispecific antibodies that engage macrophages instead of T cells](https://onco.cc/ideas/idea-bio2-myeloid-engager-bispecific/), [Deliver drugs and cells to the brain through the nose](https://onco.cc/ideas/idea-bio2-intranasal-delivery/), [Engineered immune surveillance: long-lived programmed immune cells that patrol for early cancer](https://onco.cc/ideas/idea-moon-engineered-immune-surveillance/), [Off-the-shelf natural killer cells to sweep up residual disease](https://onco.cc/ideas/idea-bio2-nk-cells-for-mrd/), [Open the barrier so engineered immune cells can enter the brain](https://onco.cc/ideas/idea-bio2-fus-for-cell-entry/), [Qualify one iPSC master cell bank once for many off-the-shelf cell products](https://onco.cc/ideas/idea-reg-ipsc-master-bank-qualified-once/)
- pathways: [Antigen presentation & immune editing](https://onco.cc/pathways/antigen-presentation-immunoediting/), [Myeloid suppression: TAMs, MDSCs & don't-eat-me signals](https://onco.cc/pathways/myeloid-suppression-axis/), [NK-cell recognition: missing self & stress ligands](https://onco.cc/pathways/nk-cell-recognition/)
- terms: [Macrophage](https://onco.cc/terms/macrophage/), [NK cell](https://onco.cc/terms/nk-cell/)
- drugs: [EB-NK-301](https://onco.cc/drugs/eb-nk-301/)
- trials: [Phase 1/2 Study of EB-NK-301 (Allogeneic TROP2-CAR NK Cells) in Advanced TROP2-Expressing Solid Tumors](https://onco.cc/trials/nct07589530/)

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