CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors - Review article

Sep 21, 2026

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Chimeric antigen receptor T-cell therapy (CAR-T) has shown strong efficacy in relapsed or refractory hematological malignancies, while CAR-natural killer (CAR-NK) therapy adds distinct benefits, including reduced safety concerns and no requirement for HLA compatibility. Despite progress in blood cancers, both modalities face major barriers in solid tumors, such as limited tumor trafficking and infiltration, together with an immunosuppressive tumor microenvironment. This review evaluates recent advances, compares CAR-NK versus CAR-T, and highlights CAR-NK engineering optimization and future directions.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Introduction

CAR-T cell cancer therapy

CAR-NK compared with CAR-T

Future perspectives

[www.nature.com/cmi](www.nature.com/cmi) REVIEW ARTICLE OPEN CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors Lei Peng1,2,12 ✉, Giacomo Sferruzza 1,2,12, Luojia Yang1,2,3,4,12, Liqun Zhou1,2,3,5 and Sidi Chen 1,2,3,4,5,6,7,8,9,10,11 ✉ © The Author(s) 2024 | | | | | --- | --- | --- | | | In the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers, demonstrating remarkable efﬁcacy in relapsed/refractory hematological malignancies in both pediatric and adult patients. CAR-natural killer (CAR-NK) cell complements CAR-T cell therapy by offering several distinct advantages. CAR-NK cells do not require HLA compatibility and exhibit low safety concerns. Moreover, CAR-NK cells are conducive to “off-the-shelf”therapeutics, providing signiﬁcant logistic advantages over CAR-T cells. Both CAR-T and CAR-NK cells have shown consistent and promising results in hematological malignancies. However, their efﬁcacy against solid tumors remains limited due to various obstacles including limited tumor trafﬁcking and inﬁltration, as well as an immuno-suppressive tumor microenvironment. In this review, we discuss the recent advances and current challenges of CAR-T and CAR-NK cell immunotherapies, with a speciﬁc focus on the obstacles to their application in solid tumors. We also analyze in depth the advantages and drawbacks of CAR-NK cells compared to CAR-T cells and highlight CAR-NK CAR optimization. Finally, we explore future perspectives of these adoptive immunotherapies, highlighting the increasing contribution of cutting-edge biotechnological tools in shaping the next generation of cellular immunotherapy. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Keywords: CAR-T; CAR-NK; Cell therapy; Cancer immunotherapy; Solid tumor | | | | | Cellular & Molecular Immunology (2024) 21:1089–1108; [https://doi.org/10.1038/s41423-024-01207-0](https://doi.org/10.1038/s41423-024-01207-0) | | | | | | INTRODUCTION Immunotherapy, which aims to stimulate the immune system to eradicate cancer, has recently revolutionized cancer treatment and constitutes the fourth cornerstone of cancer therapy alongside surgery, radiation, and chemotherapy [1, 2] . Current cancer immunotherapy research encompasses a broad range of approaches, including antibodies, vaccines, cytokines, oncolytic viruses, bi-speciﬁc molecules, and cellular therapies [3, 4] . Among these, immune checkpoint inhibitors (ICIs) and adoptive cell therapy (ACT) have emerged as the most successful immunotherapy strategies for cancer treatment [5–9] . ICIs, which block immune checkpoints, have achieved signiﬁcant tumor regression and changed standards of care for a variety of solid tumor malignancies, including melanoma, lung cancer, and head and neck cancer [5, 10, 11] . However, primary and acquired resistance remains common due to the scarcity of anti-tumor T cells and impaired memory T cells. Unlike small molecule drugs or antibodies, cells have the potential to sense and dynamically respond to diseases [12] . Cellular immunotherapy, which involves the transfer of modiﬁed immune cells back into the patient, has rapidly grown in clinical investigation and achieved signiﬁcant success in hematologic malignancies, though its use in solid tumor malignancies is still in its early stages [2, 13] . In this review, we explore the potential of CAR-T and CAR-NK cells, along with the current limitations of these treatment modalities against cancer, especially solid tumors. We present an overview of the engineering strategies implemented in recent years to address the main challenges limiting the CAR-T and CARNK cell effectiveness, showcasing the broad versatility of cellular immunotherapy. Finally, we highlight the potential advantagesand limitations of CAR-NK cells over CAR-T cells and outline the

FAQs

Why are CAR-T and CAR-NK therapies promising for cancer treatment?

CAR-T has demonstrated remarkable efficacy in relapsed or refractory hematological malignancies. CAR-NK complements CAR-T by offering advantages such as not requiring HLA compatibility and having low safety concerns.

What limits CAR-T and CAR-NK effectiveness against solid tumors?

Their efficacy remains limited by obstacles including insufficient tumor trafficking and infiltration, as well as an immunosuppressive tumor microenvironment.

What are key advantages and drawbacks of CAR-NK relative to CAR-T?

The review analyzes CAR-NK advantages and limitations compared with CAR-T in depth, emphasizing CAR-NK CAR optimization and the trade-offs between the two adoptive immunotherapy approaches.

Sep 21, 2026

Upload by Rowan