CAR-T Cell Therapy in Hematological Malignancies

Dear Colleagues,

Chimeric Antigen Receptor T-cell (CAR-T) therapy has yielded significant success in treating hematological malignancies, marking a transformative advancement in B-lineage malignancies. Despite the high initial remission induction rates, many patients continue to experience cancer recurrence, prompting the exploration of strategies to enhance immediate cancer control and improve long-term tumor suppression. The key focus to advance CAR-T cell therapy in B-lineage-derived cancers lies in improving the product quality, duration of engraftment and combinatorial targeting as well as the incorporation of complementary therapies to successfully treat patients with CD19- and BCMA antigen loss. One avenue of exploration involves identifying and optimizing CAR-T cell products to alternative target antigens. Eventually, this may lead to a broader spectrum of malignancies that can be effectively treated with CAR-T cells due to antigen expression overlap. Combinatorial strategies, integrating CAR-T therapy with other treatment modalities, are being investigated to maximize therapeutic outcomes. These strategies aim to address challenges such as antigen escape and tumor heterogeneity, which contribute to treatment resistance. The incorporation of additional effector functions, such as cytokine support in fourth-generation CAR-T, may improve the performance of CAR in a clinical context. However, the main obstacle for CAR-T cell therapy in hematological cancers remains the target antigen, as mono-targeted approaches have shown to provide cancer control in a fraction of patients with B-lineage malignancies. Novel technological innovations are required to refine the effectiveness of CAR-T cells, potentially overcoming the main reasons for CAR treatment failure. Ongoing efforts are directed towards strategies and technologies that can overcome these limitations and pave the way for its broader and more potent application in the realm of cancer therapeutics. In this Special Issue, we aim to showcase new advancements in CAR-T cell therapy for the treatment of hematological cancers, and especially want to highlight translational work in lymphoid and myeloid diseases.

Prof. Dr. Patrick Schlegel
Guest Editor

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• target validation for hematological cancers
• next-generation CAR T to overcome the TME
• combinatorial CAR therapies
• dual-targeting
• triple-targeting
• complementary CAR strategies