APR 30, 2024 7:30 AM PDT

Keynote Presentation: Targeting T-cell Malignancies with CAR-based Immunotherapy: Challenges and Potential Solutions with Live Q&A

C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Sunil S. Raikar, MD

    Assistant Professor of Pediatrics, Emory University, Aflac Cancer & Blood Disorders Center, Children's Healthcare of Atlanta, Junior Director of Graduate Studies, Molecular and Systems Pharmacology, Graduate Division of Biological and Biomedical Sciences, Emory University
    BIOGRAPHY

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has been extremely successful in treating relapsed/refractory B-cell malignancies, with six CAR T-cell products now FDA approved. Unfortunately, very limited success has been seen in translating CAR T-cell therapy for T-cell malignancies, primarily due to the lack of a cancer-specific target antigen on malignant T cells. This has resulted in several challenges in translating this innovative immunotherapy for T-cell disease: (i) CAR T cells designed against a T-cell antigen undergo fratricide (self-killing) due to the shared antigen expression on normal and malignant T cells, leading to difficulty in CAR T-cell expansion; (ii) off-tumor on-target toxicity from T-cell antigen directed CAR T cells can result in life-threatening immunosuppression from T-cell aplasia and (iii) the inability to isolate healthy T cells from a patient with a T-cell malignancy can result in product contamination, wherein malignant T cells may be inadvertently genetically modified to express the CAR, thereby making them resistant to CAR therapy. To the best of our knowledge, no tumor-specific antigen has yet been identified with universal expression on cancerous T cells, thereby hindering the development CAR T-cell therapy for this disease. Numerous approaches have been tested to address each of these challenges, such as (i) disrupting target antigen expression on CAR-modified T cells, (ii) targeting antigens with limited expression on T cells, and (iii) using third party donor cells that are either non-alloreactive or have been genome edited at the T-cell receptor α constant (TRAC) locus. In this presentation, we will discuss CAR-based approaches that have been explored both in preclinical and clinical studies targeting T-cell antigens, as well as examine other potential strategies that can be used to successfully translate this therapy for T-cell disease.

Learning Objectives: 

1. Discuss the specific challenges involved in targeting T-cell malignancies with CAR T-cell therapy.

2. Review the different strategies utilized by investigators to overcome these barriers.

3. Discuss clinical trials testing CAR T-cell therapy for T-cell malignancies.