Harnessing the potential of CAR-T cell therapy - progress, challenges, and future directions in hematological and solid tumor treatments

Sep 24, 2026

Uploaded by Jake

Traditional cancer treatments rely on nonspecific drugs and monoclonal antibodies to target tumor cells, while CAR-T cell therapy retools a patient’s T-cells to recognize and attack tumor-associated antigens. The therapy has gained regulatory approval for B-cell malignancies such as acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma via CD-19 and related targets. However, solid tumors present major barriers including limited antigen availability, hypoxic tumor cores, immunosuppressive microenvironments, elevated reactive oxygen species, and reduced T-cell infiltration. This review summarizes CAR-T evolution across hematological and solid tumors and outlines strategies such as identifying reliable antigens and using cost-effective, microenvironment-specific designs supported by single-cell RNA sequencing and artificial intelligence.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages36

Reading Time1 h 31 min

AccessFree to download

Abstract

Introduction

Traditional cancer treatment and the rise of immunotherapy

CAR-T therapy: mechanism and approvals

Blood cancers targeted via CD-19 and maturation antigens

Challenges of CAR-T in solid tumors

Antigen limitations and tumor microenvironment barriers

Strategies and future directions

Reliable antigen discovery and microenvironment-specific CAR-T design

Single-cell RNA sequencing and artificial intelligence

Dagar etal. Journal of Translational Medicine (2023) 21:449 [https://doi.org/10.1186/s12967-023-04292-3](https://doi.org/10.1186/s12967-023-04292-3) Journal of Translational Medicine REVIEW Open Access Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments Gunjan Dagar1, Ashna Gupta1, Tariq Masoodi2†, Sabah Nisar3†, Maysaloun Merhi4†, Sheema Hashem5, Ravi Chauhan1, Manisha Dagar6, Sameer Mirza7, Puneet Bagga3, Rakesh Kumar8, Ammira S. Al‑Shabeeb Akil9, Muzafar A. Macha 10, Mohammad Haris 11,12, Shahab Uddin12,13*, Mayank Singh1* and Ajaz A. Bhat9* Abstract Traditional cancer treatments use nonspecific drugs and monoclonal antibodies to target tumor cells. Chimeric antigen receptor (CAR)‑T cell therapy, however, leverages the immune system’sT‑cells to recognize and attack tumor cells. T‑cells are isolated from patients and modified to target tumor‑associated antigens. CAR‑T therapy has achieved FDA approval for treating blood cancers like B‑cell acute lymphoblastic leukemia, large B‑cell lymphoma, and multi‑ ple myeloma by targeting CD‑19 and B‑cell maturation antigens. Bi‑specific chimeric antigen receptors may con‑ tribute to mitigating tumor antigen escape, but their efficacy could be limited in cases where certain tumor cells do not express the targeted antigens. Despite success in blood cancers, CAR‑T technology faces challenges in solid tumors, including lack of reliable tumor‑associated antigens, hypoxic cores, immunosuppressive tumor environments, enhanced reactive oxygen species, and decreased T‑cell infiltration. To overcome these challenges, current research aims to identify reliable tumor‑associated antigens and develop cost‑effective, tumor microenvironment‑specific CAR‑T cells. This review covers the evolution of CAR‑T therapy against various tumors, including hematological and solid tumors, highlights challenges faced by CAR‑T cell therapy, and suggests strategies to overcome these obsta‑ cles, such as utilizing single‑cell RNA sequencing and artificial intelligence to optimize clinical‑grade CAR‑T cells. †Tariq Masoodi, Sabah Nisar and Maysaloun Merhi have contributed equally. *Correspondence: Shahab Uddin[skhan34@hamad.qa](skhan34@hamad.qa)[ ](skhan34@hamad.qa)Mayank Singh [mayank.osu@gmail.com](mayank.osu@gmail.com)[ ](mayank.osu@gmail.com)Ajaz A. Bhat[abhat@sidra.org](abhat@sidra.org) 1 Department of Medical Oncology (Lab.), Dr. BRAIRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, Delhi 110029, India 2 Laboratory of Cancer Immunology and Genetics, Sidra Medicine, Doha, Qatar 3 Department of Diagnostic Imaging, St. Jude Children’s Research Hospital, Memphis, TN, USA 4 National Center for Cancer Care and Research, Hamad Medical Corporation, 3050 Doha, Qatar 5 Department of Human Genetics, Sidra Medicine, Doha, Qatar 6 Shiley Eye Institute, University of California San Diego, San Diego, CA, USA 7 Department of Chemistry, College of Sciences, United Arab Emirates University, Al‑Ain, United Arab Emirates 8 School of Biotechnology, Shri Mata Vaishno Devi University, Katra, Jammu and Kashmir 182320, India 9 Department of Human Genetics‑Precision Medicine in Diabetes, Obesity and Cancer Program, Sidra Medicine, P. O. Box 26999, Doha, Qatar 10 Watson‑Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Pulwama, Jammu and Kashmir, India 11 Center for Advanced Metabolic Imaging in Precision Medicine, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA 12 Laboratory Animal Research Center, Qatar University, Doha, Qatar 13 Translational Research Institute, Academic Health System, Hamad Medical Corporation, P. O. Box 3050, Doha, Qatar © The Author(s) 2023, corrected publication 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use,

FAQs

How does CAR-T cell therapy differ from traditional cancer treatments?

Traditional therapies use nonspecific drugs and monoclonal antibodies, whereas CAR-T therapy modifies a patient’s T-cells to recognize and attack tumor cells using chimeric antigen receptors.

Which blood cancers have CAR-T therapies been approved to treat, and what targets are involved?

CAR-T has FDA approval for blood cancers including B-cell acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma, typically targeting CD-19 and B-cell maturation antigens.

What are the main challenges of CAR-T cell therapy in solid tumors?

Key challenges include lack of reliable tumor-associated antigens, hypoxic tumor cores, immunosuppressive microenvironments, increased reactive oxygen species, and decreased T-cell infiltration.

Sep 24, 2026

Uploaded by Jake