Chimeric antigen receptor T-cell therapy for melanoma

ABSTRACT

Introduction

In recent years, chimeric antigen receptor (CAR) T cell therapy has emerged as a cancer treatment. After initial therapeutic success for hematologic malignancies, this approach has been extended for the treatment of solid tumors including melanoma.

Areas covered

T cells need to be reprogramed to recognize specific antigens expressed only in tumor cells, a difficult problem since cancer cells are simply transformed normal cells. Tumor antigens, namely, CSPG4, CD70, and GD2 have been targeted by CAR-T cells for melanoma. Moreover, different co-stimulatory signaling domains need to be selected to direct T cell fate. In this review, various approaches for the treatment of melanoma and their effectiveness are comprehensively reviewed and the current status, challenges, and future perspective of CAR-T cell therapy for melanoma are discussed. Literature search was accomplished in three databases (PubMed, Google scholar, and Clinicaltrials.gov). Published papers and clinical trials were screened and relevant documents were included by checking pre-defined eligibility criteria.

Expert opinion

Despite obstacles and the risk of adverse events, CAR T cell therapy could be used for patients with treatment-resistant cancer. Clinical trials are underway to determine the efficacy of this approach for the treatment of melanoma.

KEYWORDS:

• Adoptive Cell Therapy
• cutaneous Melanoma
• immunotherapy
• malignant Melanoma
• treatment

Article highlights

• Melanoma is the deadliest of skin cancers.

• There are several therapeutic options for melanoma which have not reached the maximum efficacy.

• CAR T cell therapy is a type of ACT which showed efficacy in animal models for tumor cells resistant to other approaches.

• CAR T cell has limited efficacy for solid tumors.

• Choosing an accessible and stable tumor antigen and potent costimulatory molecules is necessary to improve the outcome.

• Several antigens including GD2, CD20, CD70, gp100, NY-ESO-1, B7-H3, and VEGFR-2 have been tested for targeting by CAR T cells for melanoma treatment in clinical studies.

• The results of currently ongoing clinical trials to assess CAR T cell will determine its efficacy for melanoma.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.