Patient selection for CAR T or BiTE therapy in multiple myeloma: Which treatment for each patient?

Kegyes, David; Constantinescu, Cătălin; Vrancken, Louise; Rasche, Leo; Gregoire, Celine; Tigu, Bogdan; Gulei, Diana; Dima, Delia; Tănase, Alina; Einsele, Hermann; Ciurea, Stefan O.; Tomuleasa, Ciprian; Caers, Jo

doi:10.1186/s13045-022-01296-2

Cited by 29 publications

(26 citation statements)

References 143 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD138 is a specific biomarker for plasma cells. Reported data demonstrated the safety and modest therapeutic response of CD138‐CAR‐T cells 25,26 …”

Section: Discussionmentioning

confidence: 99%

A second‐generation CD38‐CAR‐T cell for the treatment of multiple myeloma

et al. 2023

Cancer Medicine

View full text Add to dashboard Cite

Background Multiple myeloma (MM) is an aggressive plasma cell malignancy, causing a number of deaths worldwide every year. Chimeric antigen receptor (CAR) transduced T‐cell therapy has been a promising immunotherapy against hematological malignancies. Methods In this study, we developed a second‐generation CAR construct and generated CAR‐T cells targeting CD38 molecule. Then effects of CAR‐T cells against MM cell lines were evaluated. Results CD38‐CAR‐T cells showed higher cytotoxicity to MM cell lines and primary MM cells than that of control T cells in vitro. Over 50% MM1.s and RPMI8226 cells were killed by CAR‐T cells even at effector to target ratio of 1:100. CAR‐T cells also showed an enhanced cytotoxicity against primary MM cells. CAR‐T cells could be activated and produced a variety of cytokines in a target‐dependent manner. In vivo test indicated that CAR‐T cells also showed significant antitumor effect on xenograft mice models. Conclusion These results indicated a promising therapeutic strategy of CD38‐CAR‐T cells against MM.

show abstract

“…CD138 is a specific biomarker for plasma cells. Reported data demonstrated the safety and modest therapeutic response of CD138‐CAR‐T cells 25,26 …”

Section: Discussionmentioning

confidence: 99%

A second‐generation CD38‐CAR‐T cell for the treatment of multiple myeloma

et al. 2023

Cancer Medicine

View full text Add to dashboard Cite

show abstract

“…Engineering chimeric antigen receptor (CAR)-T cells with tumor specificity have made impressive success in the treatment of patients with hematologic malignancies [169][170][171][172][173][174]. However, the efficacy of CAR-T therapy in many solid tumors remains poor.…”

Section: In Vivo Delivery Of Rlr-activating Rna By Nanoparticles Extr...mentioning

confidence: 99%

Exploiting RIG-I-like receptor pathway for cancer immunotherapy

et al. 2023

View full text Add to dashboard Cite

RIG-I-like receptors (RLRs) are intracellular pattern recognition receptors that detect viral or bacterial infection and induce host innate immune responses. The RLRs family comprises retinoic acid-inducible gene 1 (RIG-I), melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2) that have distinctive features. These receptors not only recognize RNA intermediates from viruses and bacteria, but also interact with endogenous RNA such as the mislocalized mitochondrial RNA, the aberrantly reactivated repetitive or transposable elements in the human genome. Evasion of RLRs-mediated immune response may lead to sustained infection, defective host immunity and carcinogenesis. Therapeutic targeting RLRs may not only provoke anti-infection effects, but also induce anticancer immunity or sensitize “immune-cold” tumors to immune checkpoint blockade. In this review, we summarize the current knowledge of RLRs signaling and discuss the rationale for therapeutic targeting RLRs in cancer. We describe how RLRs can be activated by synthetic RNA, oncolytic viruses, viral mimicry and radio-chemotherapy, and how the RNA agonists of RLRs can be systemically delivered in vivo. The integration of RLRs agonism with RNA interference or CAR-T cells provides new dimensions that complement cancer immunotherapy. Moreover, we update the progress of recent clinical trials for cancer therapy involving RLRs activation and immune modulation. Further studies of the mechanisms underlying RLRs signaling will shed new light on the development of cancer therapeutics. Manipulation of RLRs signaling represents an opportunity for clinically relevant cancer therapy. Addressing the challenges in this field will help develop future generations of cancer immunotherapy.

show abstract

“…Genetic abnormities, mostly translocation and hyper-diploidy, result in dysregulated cancer-immunity cycle that allows MM to escape immune surveillance with an uncontrolled cell proliferation ( 4 , 5 ). The past two decades have significantly refashioned the therapeutic options of MM, such as the availability of proteasome inhibitors (PI), immunomodulatory drugs (IMiDs), histone deacetylase inhibitors (HDACi), anti-CD38 monoclonal antibodies (mABs), antibody-drug conjugates (ADC), and selective inhibitors nuclear export (SINE) ( 6 ). However, MM remains incurable for most patients, as persistent clonal evolution drives new mutations which confer MM high-risk signatures and resistance to standard care ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

Chimeric antigen receptor T-cell therapy for multiple myeloma

et al. 2022

View full text Add to dashboard Cite

Multiple myeloma (MM) is a malignant plasma cell disorder that remains incurable for most patients, as persistent clonal evolution drives new mutations which confer MM high-risk signatures and resistance to standard care. The past two decades have significantly refashioned the therapeutic options for MM, especially adoptive T cell therapy contributing to impressive response rate and clinical efficacy. Despite great promises achieved from chimeric antigen receptor T-cell (CAR-T) therapy, the poor durability and severe toxicity (cytokine release syndrome and neurotoxicity) are still huge challenges. Therefore, relapsed/refractory multiple myeloma (RRMM), characterized by the nature of clinicopathologic and molecular heterogeneity, is frequently associated with poor prognosis. B Cell Maturation Antigen (BCMA) is the most successful target for CAR-T therapy, and other potential targets either for single-target or dual-target CAR-T are actively being studied in numerous clinical trials. Moreover, mechanisms driving resistance or relapse after CAR-T therapy remain uncharacterized, which might refer to T-cell clearance, antigen escape, and immunosuppressive tumor microenvironment. Engineering CAR T-cell to improve both efficacy and safety continues to be a promising area for investigation. In this review, we aim to describe novel tumor-associated neoantigens for MM, summarize the data from current MM CAR-T clinical trials, introduce the mechanism of disease resistance/relapse after CAR-T infusion, highlight innovations capable of enhanced efficacy and reduced toxicity, and provide potential directions to optimize manufacturing processes.

show abstract

Patient selection for CAR T or BiTE therapy in multiple myeloma: Which treatment for each patient?

Cited by 29 publications

References 143 publications

A second‐generation CD38‐CAR‐T cell for the treatment of multiple myeloma

A second‐generation CD38‐CAR‐T cell for the treatment of multiple myeloma

Exploiting RIG-I-like receptor pathway for cancer immunotherapy

Chimeric antigen receptor T-cell therapy for multiple myeloma

Contact Info

Product

Resources

About