CAR T Cell Therapy: A New Weapon to Fight Bladder Cancer

Document Type : Editorial

Author

Department of Stem Cells Technology and Tissue Regeneration, School of Biology, College of Science, University of Tehran, Tehran, Iran

Abstract

It has been a while since chimeric antigen receptor (CAR)-T cell therapy was introduced as an attractive immunotherapeutic approach to fighting cancer. Despite the remarkable success of this approach in treating blood malignancies such as acute lymphoblastic leukemia (ALL), treatment of solid cancers such as bladder cancer still has many challenges and problems. This work highlights CAR-based cell therapy's preclinical and clinical studies in bladder cancer, their successes, and the challenges involved in translating this procedure into the clinic.

Highlights

  • CAR-T cell therapy as a super promising immunotherapy approach has opened new gates for the treatment of cancers.
  • Despite the challenges of this method in the treatment of solid cancers such as bladder cancer, there is still an attempt to smooth the way.
  • CAR-based therapies for bladder cancers have entered the clinical trials and could be the future for treating this type of cancer if the challenges are overcome.

Keywords

Main Subjects


Editorial: It has been ten years since Emily Whitehead (the first child in the world who received engineered T cells) was cancer-free. The girl lived thanks to CAR-T cell therapy.

CAR T-cell therapy is a brilliant immunotherapy approach in which a patient's T cells are harvested from the body and genetically engineered to express a chimeric antigen receptor against a tumor-associated or tumor-specific antigen. These cells are then returned to the patient's body to attack cancer cells and eradicate them. This method was first used to treat ALL and had promising results (1). To date, the FDA has approved five CAR T-cell products, all of which are for blood malignancies. This treatment generally has more favorable effects on liquid tumors than solid ones. Solid tumors are highly resistant to this treatment due to their complex organization (acidic and hypoxic core) and the establishment of an immunosuppressive niche. A tremendous amount of research has been done and continues to be done to overcome the challenges of CAR-T cell therapy in solid cancers. So far, no CAR-T cell-based therapy product has been approved by the FDA, but many clinical trials are underway, and the number is growing.

Bladder cancer, the second most common urological malignancy in terms of prevalence and mortality, does not fully respond to standard treatments such as surgery, chemotherapy, radiotherapy, and immunotherapy with bacillus Calmette-guérin (BCG). Therefore, there is still a demand for new and more effective treatments for bladder cancer, and CAR-T cell therapy can be one of the best options for this purpose.

Preclinical studies of T cell therapy for bladder cancer have shown that this immunotherapy can effectively treat bladder cancer. In a study by Grunewald et al., The effect of combining CAR T cells against Human EGFR and CD44V6 with Decitabine (a DNA methyltransferase inhibitor) was investigated. Their results showed that T cells could kill bladder cancer cells, and this cytotoxic effect was enhanced by adding Decitabine(2).

CAR-T cells can be helpful in personal medicine to overcome the heterogeneity and genetic instability of bladder cancer. In a study by Yu et al., The effect of CAR-T cells against MUC1 antigen on patient-derived bladder cancer organoids was investigated. CAR-T cells could identify tumor cells and destroy them (3).

 To date, 4 CAR-dependent immunotherapy clinical trials for bladder cancer have been reported in early stages (according to Clinicaltrials.gov). In these trials, T lymphocytes and macrophages were used as CAR carriers (Table 1).

 

Table 1. Clinical trials of CAR-based immunotherapies for bladder cancer

Trial Number

Status

Phase

Cell type

Antigenes

NCT03185486

Unknown

I/II

T lymphocyte

PSMA FRa

NCT03960060

Active, not recruiting

I

T lymphocyte

ROR2

NCT03740256

Recruiting

I

T lymphocyte

HER2

NCT04660939

Recruiting

I

T lymphocyte

HER2

 

Conclusion 

CAR-T cell therapy could be an excellent candidate for fighting bladder cancer in the future by overcoming the challenges of this approach in solid tumors such as on-target off-tumor toxicity, cytokine release syndrome (CRS), graft versus host disease (GVHD), and antigen escaping.

 

Acknowledgments

There are no acknowledgments to declare.

 

Conflict of Interest

The author declares that there is no conflict of interest.

 

Funding

None.

 

Ethical statement

Not applicable.

 

Data Availability

Data will be provided on request.

 

Abbreviations

ALL                Acute lymphoblastic leukemia

BCG                Bacillus calmette-guérin

CAR                Chimeric antigen receptor

CRS                 Cytokine release syndrome

GVHD             Graft versus host disease

1.   Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG, et al. CD19-Targeted T Cells Rapidly Induce Molecular Remissions in Adults with Chemotherapy-Refractory Acute Lymphoblastic Leukemia. Science Translational Medicine. 2013;5(177):177ra38-ra38.
2.   Grunewald CM, Haist C, König C, Petzsch P, Bister A, Nößner E, et al. Epigenetic Priming of Bladder Cancer Cells With Decitabine Increases Cytotoxicity of Human EGFR and CD44v6 CAR Engineered T-Cells. Frontiers in Immunology. 2021;12.
3.   Yu L, Li Z, Mei H, Li W, Chen D, Liu L, et al. Patient-derived organoids of bladder cancer recapitulate antigen expression profiles and serve as a personal evaluation model for CAR-T cells in vitro. Clinical & translational immunology. 2021;10(2):e1248.
Volume 4, Issue 2
April 2022
Pages 54-56
  • Receive Date: 02 May 2022
  • Revise Date: 15 May 2022
  • Accept Date: 21 June 2022
  • First Publish Date: 21 June 2022