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Challenges and strategies in relation to effective CAR-T cell immunotherapy for solid tumors

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Abstract

Chimeric Antigen Receptor T cell (CAR-T) therapy has revolutionized cancer treatment, but its application to solid tumors is limited. CAR-T cells have poor incapability of entering, surviving, proliferating, and finally exerting function in the tumor microenvironment. This review summarizes the main strategies related to enhancing the infiltration, efficacy, antigen recognition, and production of CAR-T in solid tumors. Additional applications of CAR-γδ T and macrophages are also discussed. We believe CAR-T will be a milestone in treating solid tumors once these problems are solved.

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Data availability

The articles analyzed during the current study are available in the literature and listed in the references.

Abbreviations

CAR:

Chimeric antigen receptor

scFv:

Single-chain fragment variable

TAA:

Tumor-associated antigen

TME:

Tumor microenvironment

MDSC:

Myeloid-derived suppressor cell

HRE:

Hypoxia response element

PSMA:

Prostate-specific membrane antigen

CCL2:

C–C motif chemokine ligand 2

DC:

Dendritic cells

CXCL12:

C-X-C motif chemokine ligand 12

CSF1:

Colony-stimulating factor 1

VEGF:

Vascular endothelial growth factor

CAR-M:

CAR-engineered macrophages

CSR:

Chimeric switch receptor

PD1:

Programmed death-1

CEA:

Carcinoembryonic antigen

TAM:

Tumor-associated macrophages

PDAC:

Pancreatic ductal adenocarcinoma

iCAR:

Inhibitory CAR

PSCA:

Prostate stem cell antigen

TRUCK:

T cells redirected for universal cytokine-mediated killing

ZOL:

Zoledronate

CAIX:

Carbonic anhydrase IX

iPSC:

Induced pluripotent stem cell

HPSE:

Expression of heparinase

ECM:

Extracellular matrix

CAF:

Cancer-associated fibroblasts

FAP:

Fibroblast activation protein

DNR:

Dominant-negative receptors

synNotch:

Synthetic Notch receptor

SDF-1α:

Secrete stromal cell-derived factor 1α

CRS:

Cytokine Release Syndrome

CCR:

Chimeric costimulatory receptor

TSAs:

Tumor-specific antigens

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Funding

This work was supported by the National Natural Science Foundation of China (31870899 and 32070899 to X.Z.).

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Author notes

  1. Guangxun Yuan and Mengke Ye have contributed equally to this study.

Authors and Affiliations

  1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China

    Guangxun Yuan, Mengke Ye, Yixi Zhang & Xun Zeng

Authors
  1. Guangxun Yuan
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  2. Mengke Ye
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  3. Yixi Zhang
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  4. Xun Zeng
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Contributions

GXY, MKY and XZ wrote the main manuscript text and YXZ prepared Figs. 1 and 2. All authors reviewed the manuscript.

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Correspondence to Yixi Zhang or Xun Zeng.

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Yuan, G., Ye, M., Zhang, Y. et al. Challenges and strategies in relation to effective CAR-T cell immunotherapy for solid tumors. Med Oncol 41, 126 (2024). https://doi.org/10.1007/s12032-024-02310-y

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