{"entity":{"id":"car-nk-macrophage","kind":"technology","name":"CAR-NK & CAR-macrophage","aka":["CAR-NK","CAR-NK cells","CAR-macrophage"],"tldr":"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.","status":"phase-1","asOf":"2026-09-04","links":[{"label":"Liu et al., CAR-transduced natural killer cells in CD19-positive lymphoid tumours (NEJM 2020)","url":"https://doi.org/10.1056/NEJMoa1910607"},{"label":"Klichinsky et al., Human chimeric antigen receptor macrophages for cancer immunotherapy (Nature Biotechnology 2020)","url":"https://doi.org/10.1038/s41587-020-0462-y"}],"tags":["frontier"],"related":["nk-cell-therapy"],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t","allogeneic-cell-therapy"],"targets":[],"drugs":[],"companies":["indapta-therapeutics","onk-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-klichinsky-nat-biotechnol","paper-liu-n-engl-j-med"],"journals":[],"dependsOn":["viral-vector-manufacturing","cell-therapy-release-testing"],"notes":[],"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"]},"route":"/technologies/car-nk-macrophage/","neighbours":{"technology":[{"id":"allogeneic-cell-therapy","kind":"technology","name":"Allogeneic (off-the-shelf) cell therapy","route":"/technologies/allogeneic-cell-therapy/"},{"id":"allogeneic-cell-banks","kind":"technology","name":"Allogeneic cell banks: one donor, hundreds of doses","route":"/technologies/allogeneic-cell-banks/"},{"id":"allogeneic-cell-banking","kind":"technology","name":"Allogeneic donor and iPSC master cell banks","route":"/technologies/allogeneic-cell-banking/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"cell-therapy-release-testing","kind":"technology","name":"Cell-therapy release and potency testing","route":"/technologies/cell-therapy-release-testing/"},{"id":"nk-cell-therapy","kind":"technology","name":"NK cell therapy and CAR-NK","route":"/technologies/nk-cell-therapy/"},{"id":"trained-innate-immunity","kind":"technology","name":"Trained innate immunity","route":"/technologies/trained-innate-immunity/"},{"id":"viral-vector-manufacturing","kind":"technology","name":"Viral vector manufacturing (lentiviral, retroviral, AAV)","route":"/technologies/viral-vector-manufacturing/"}],"section":[{"id":"cell-therapy","kind":"section","name":"Cell Therapy","route":"/fronts/cell-therapy/"}],"company":[{"id":"fate-therapeutics","kind":"company","name":"Fate Therapeutics","route":"/companies/fate-therapeutics/"},{"id":"indapta-therapeutics","kind":"company","name":"Indapta Therapeutics","route":"/companies/indapta-therapeutics/"},{"id":"nkarta","kind":"company","name":"Nkarta","route":"/companies/nkarta/"},{"id":"onk-therapeutics","kind":"company","name":"ONK Therapeutics","route":"/companies/onk-therapeutics/"}],"paper":[{"id":"paper-klichinsky-nat-biotechnol","kind":"paper","name":"Human chimeric antigen receptor macrophages for cancer immunotherapy","route":"/key-papers/paper-klichinsky-nat-biotechnol/"},{"id":"paper-liu-n-engl-j-med","kind":"paper","name":"Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors","route":"/key-papers/paper-liu-n-engl-j-med/"}],"institution":[{"id":"humanitas","kind":"institution","name":"IRCCS Humanitas Research Hospital","route":"/institutions/humanitas/"},{"id":"kyoto-university-hospital","kind":"institution","name":"Kyoto University Hospital","route":"/institutions/kyoto-university-hospital/"},{"id":"minnesota-masonic","kind":"institution","name":"Masonic Cancer Center, University of Minnesota","route":"/institutions/minnesota-masonic/"},{"id":"md-anderson","kind":"institution","name":"MD Anderson Cancer Center","route":"/institutions/md-anderson/"},{"id":"qimr-berghofer","kind":"institution","name":"QIMR Berghofer Medical Research Institute","route":"/institutions/qimr-berghofer/"}],"roadmap":[{"id":"cell-therapy-roadmap","kind":"roadmap","name":"Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR","route":"/roadmaps/cell-therapy-roadmap/"}],"person":[{"id":"hans-gustaf-ljunggren","kind":"person","name":"Hans-Gustaf Ljunggren","route":"/people/hans-gustaf-ljunggren/"},{"id":"katy-rezvani","kind":"person","name":"Katayoun Rezvani","route":"/people/katy-rezvani/"},{"id":"michael-caligiuri","kind":"person","name":"Michael A. Caligiuri","route":"/people/michael-caligiuri/"},{"id":"rolf-kiessling","kind":"person","name":"Rolf Kiessling","route":"/people/rolf-kiessling/"}],"bottleneck":[{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","route":"/bottlenecks/b-manufacturing-cell-therapy/"}],"idea":[{"id":"idea-bio2-myeloid-engager-bispecific","kind":"idea","name":"Bispecific antibodies that engage macrophages instead of T cells","route":"/ideas/idea-bio2-myeloid-engager-bispecific/"},{"id":"idea-bio2-intranasal-delivery","kind":"idea","name":"Deliver drugs and cells to the brain through the nose","route":"/ideas/idea-bio2-intranasal-delivery/"},{"id":"idea-moon-engineered-immune-surveillance","kind":"idea","name":"Engineered immune surveillance: long-lived programmed immune cells that patrol for early cancer","route":"/ideas/idea-moon-engineered-immune-surveillance/"},{"id":"idea-bio2-nk-cells-for-mrd","kind":"idea","name":"Off-the-shelf natural killer cells to sweep up residual disease","route":"/ideas/idea-bio2-nk-cells-for-mrd/"},{"id":"idea-bio2-fus-for-cell-entry","kind":"idea","name":"Open the barrier so engineered immune cells can enter the brain","route":"/ideas/idea-bio2-fus-for-cell-entry/"},{"id":"idea-reg-ipsc-master-bank-qualified-once","kind":"idea","name":"Qualify one iPSC master cell bank once for many off-the-shelf cell products","route":"/ideas/idea-reg-ipsc-master-bank-qualified-once/"}],"pathway":[{"id":"antigen-presentation-immunoediting","kind":"pathway","name":"Antigen presentation & immune editing","route":"/pathways/antigen-presentation-immunoediting/"},{"id":"myeloid-suppression-axis","kind":"pathway","name":"Myeloid suppression: TAMs, MDSCs & don't-eat-me signals","route":"/pathways/myeloid-suppression-axis/"},{"id":"nk-cell-recognition","kind":"pathway","name":"NK-cell recognition: missing self & stress ligands","route":"/pathways/nk-cell-recognition/"}],"term":[{"id":"macrophage","kind":"term","name":"Macrophage","route":"/terms/macrophage/"},{"id":"nk-cell","kind":"term","name":"NK cell","route":"/terms/nk-cell/"}],"drug":[{"id":"eb-nk-301","kind":"drug","name":"EB-NK-301","route":"/drugs/eb-nk-301/"}],"trial":[{"id":"nct07589530","kind":"trial","name":"Phase 1/2 Study of EB-NK-301 (Allogeneic TROP2-CAR NK Cells) in Advanced TROP2-Expressing Solid Tumors","route":"/trials/nct07589530/"}]}}