A Bright Horizon: Immunotherapy for Pediatric T-Cell Malignancies

Abstract

Immunotherapy has transformed the treatment of hematologic malignancies in the past two decades. The treatment of acute lymphoblastic leukemia (ALL), in particular, has been highly impacted by multiple novel immunotherapies. For pediatric patients with T-cell malignancies, translating immunotherapies has proved more challenging due to the complexities of fratricide, risk of product contamination with malignant cells, and concerns over T-cell aplasia. Despite these hurdles, many creative and promising strategies are on the horizon. We review challenges in the development of immunotherapy for T-cell malignancies, strategies to overcome these challenges, as well as therapies currently being investigated and starting to reach the clinic. Immunotherapy will hopefully successfully treat patients with relapsed and refractory T-cell malignancies and may someday be incorporated in up-front protocols in order to prevent relapses.

Broadening the horizon: potential applications of CAR-T cells beyond current indications

“…There are particular target antigens for different patient populations like targets specifically investigated for pediatric T-cell malignancies ( 75 ). Today, many of these targets seem promising, but CD7 is still the most extensively tested CAR-T-cell target antigen in clinical trials.…”

Mediastinal tumor: thymoma or lymphoma?

“…Patient stratification based on immunogenetic analysis reveals the possibility of using novel strategies including immunotherapies. Individualized treatment is crucial for patients with relapsed and refractory T-cell malignancies [10].…”

Advances, Limitations and Future Challenges in the Management of Immunotherapy for Hematological Diseases and Solid Tumors

“…Despite the mentionable success in the B-cell and T-cell ALL or anaplastic large cell lymphoma in the primary or secondary (in the case of recurrence) therapy setting, the response to immunotherapeutic treatment cannot be guaranteed at the time point of therapy initiation, and it is associated with a relatively high rate of relapse. The authors Newman and Teaschey describe the challenges of translating immunotherapies for pediatric patients with T-cell malignancies, which were not expected initially [12]. These include therapy resistances, complexities of the self-killing of the chimeric antigen receptor (CAR) T-cells, risk of product contamination with malignant cells, the potential toxicity of T-cell aplasia, graft versus host disease and immunotherapy side effects, such as cytokine release syndrome.…”