» Articles » PMID: 38673757

Car T Cells in Solid Tumors: Overcoming Obstacles

Abstract

Chimeric antigen receptor T cell (CAR T cell) therapy has emerged as a prominent adoptive cell therapy and a therapeutic approach of great interest in the fight against cancer. This approach has shown notorious efficacy in refractory hematological neoplasm, which has bolstered its exploration in the field of solid cancers. However, successfully managing solid tumors presents considerable intrinsic challenges, which include the necessity of guiding the modified cells toward the tumoral region, assuring their penetration and survival in adverse microenvironments, and addressing the complexity of identifying the specific antigens for each type of cancer. This review focuses on outlining the challenges faced by CAR T cell therapy when used in the treatment of solid tumors, as well as presenting optimizations and emergent approaches directed at improving its efficacy in this particular context. From precise localization to the modulation of the tumoral microenvironment and the adaptation of antigen recognition strategies, diverse pathways will be examined to overcome the current limitations and buttress the therapeutic potential of CAR T cells in the fight against solid tumors.

Citing Articles

Chimeric Antigen Receptor Cell Therapy: Empowering Treatment Strategies for Solid Tumors.

Jaing T, Hsiao Y, Wang Y Curr Issues Mol Biol. 2025; 47(2).

PMID: 39996811 PMC: 11854309. DOI: 10.3390/cimb47020090.


Targeting refractory diffuse large B cell lymphoma by CAR-WEE1 T-cells: In vitro evaluation.

Ahmed H, Moselhy S, Mohamad M, Soliman A, Hassan M, El-Khazragy N Ann Hematol. 2025; .

PMID: 39820427 DOI: 10.1007/s00277-024-06134-8.


Vδ2 T-cell engagers bivalent for Vδ2-TCR binding provide anti-tumor immunity and support robust Vγ9Vδ2 T-cell expansion.

King L, de Jong M, Veth M, Hulsik D, Yousefi P, Iglesias-Guimarais V Front Oncol. 2024; 14:1474007.

PMID: 39493452 PMC: 11527600. DOI: 10.3389/fonc.2024.1474007.


Challenges in validation of combination treatment strategies for CRC using patient-derived organoids.

Benboubker V, Ramzy G, Jacobs S, Nowak-Sliwinska P J Exp Clin Cancer Res. 2024; 43(1):259.

PMID: 39261955 PMC: 11389238. DOI: 10.1186/s13046-024-03173-x.


The next frontier in immunotherapy: potential and challenges of CAR-macrophages.

Li J, Chen P, Ma W Exp Hematol Oncol. 2024; 13(1):76.

PMID: 39103972 PMC: 11302330. DOI: 10.1186/s40164-024-00549-9.


References
1.
Long L, Zhang X, Chen F, Pan Q, Phiphatwatchara P, Zeng Y . The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy. Genes Cancer. 2019; 9(5-6):176-189. PMC: 6305110. DOI: 10.18632/genesandcancer.180. View

2.
Maude S, Laetsch T, Buechner J, Rives S, Boyer M, Bittencourt H . Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018; 378(5):439-448. PMC: 5996391. DOI: 10.1056/NEJMoa1709866. View

3.
Abken H . Driving CARs on the Highway to Solid Cancer: Some Considerations on the Adoptive Therapy with CAR T Cells. Hum Gene Ther. 2017; 28(11):1047-1060. DOI: 10.1089/hum.2017.115. View

4.
Jahn L, Hagedoorn R, van der Steen D, Hombrink P, Kester M, Schoonakker M . A CD22-reactive TCR from the T-cell allorepertoire for the treatment of acute lymphoblastic leukemia by TCR gene transfer. Oncotarget. 2016; 7(44):71536-71547. PMC: 5342099. DOI: 10.18632/oncotarget.12247. View

5.
Yolcu E, Shirwan H, Askenasy N . Fas/Fas-Ligand Interaction As a Mechanism of Immune Homeostasis and β-Cell Cytotoxicity: Enforcement Rather Than Neutralization for Treatment of Type 1 Diabetes. Front Immunol. 2017; 8:342. PMC: 5366321. DOI: 10.3389/fimmu.2017.00342. View