A34 Daratumumab Dose Dependent Liver Injury

Altuwaijri, Mansour; Lam, Eric

doi:10.1093/jcag/gwy008.035

Cited by 2 publications

(1 citation statement)

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“…In clinical studies, administration of Daratumumab, an anti‐CD38 monoclonal antibody, showed little or no toxicity at moderate doses, but led to increased risk of liver damage at high doses. [ 13 ] An appealing and more specific immunotherapy strategy for MM was proposed via the adoptive transfer of CD38‐targeting cytotoxic T cells. [ 14 ] One major concern in CD38‐targeted therapy is the wide expression of CD38 in a range of different tissues.…”

Section: Introductionmentioning

confidence: 99%

Avidity‐Based Selection of Tissue‐Specific CAR‐T Cells from a Combinatorial Cellular Library of CARs

Ren

Zhang

et al. 2021

Advanced Science

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Using T‐cell chimeric antigen receptors (CAR‐T) to activate and redirect T cells to tumors expressing the cognate antigen represents a powerful approach in cancer therapy. However, normal tissues with low expression of tumor‐associated antigens (TAAs) can be mistargeted, resulting in severe side effects. An approach using a collection of T cells expressing a diverse, 106‐member combinatorial cellular library of CARs, in which members can be specifically enriched based on avidity for cell membrane antigens, is reported. Using CD38 as the target antigen, an efficient and effective selection of CARs specifically recognizing CD38+ tumor cells is demonstrated. These selected CAR‐T's produce cytokines known to be associated with T cell activation in a CD38 expression‐dependent manner. This avidity‐based selection endows the engineered T cells with minimal off‐tumor effects, while retaining robust antitumor efficacy both in vitro and in vivo. The described method may facilitate the application of CAR‐T therapy to TAAs previously considered undruggable.

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Section: Introductionmentioning

confidence: 99%