Vγ9Vδ2 T cells expressing a BCMA—Specific chimeric antigen receptor inhibit multiple myeloma xenograft growth

Zhang, Xi; Ng, Yi Zhen; Du, Zhicheng; Li, Zhendong; Chen, Can; Xiao, Lin; Chng, Wee Joo; Wang, Shu

doi:10.1371/journal.pone.0267475

Cited by 5 publications

(2 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, some of these approaches are also relevant to products relying on genetic manipulation of the native TCR itself ( 150 – 152 ). Finally, some of these BCMA-specific innovations may be applicable to other types of CAR-transduced lymphocytes as well: for example, Natural Killer cells, invariant NK T cells, and gamma-delta T cells ( 153 – 156 ).…”

Section: Discussionmentioning

confidence: 99%

Innovation in BCMA CAR-T therapy: Building beyond the Model T

2022

View full text Add to dashboard Cite

Autologous chimeric antigen receptor T-cell (CAR-T) therapies targeting B-cell maturation antigen (BCMA) have revolutionized the field of multiple myeloma in the same way that the Ford Model T revolutionized the original CAR world a century ago. However, we are only beginning to understand how to improve the efficacy and usability of these cellular therapies. In this review, we explore three automotive analogies for innovation with BCMA CAR-T therapies: stronger engines, better mileage, and hassle-free delivery. Firstly, we can build stronger engines in terms of BCMA targeting: improved antigen binding, tools to modulate antigen density, and armoring to better reach the antigen itself. Secondly, we can improve “mileage” in terms of response durability through ex vivo CAR design and in vivo immune manipulation. Thirdly, we can implement hassle-free delivery through rapid manufacturing protocols and off-the-shelf products. Just as the Model T set a benchmark for car manufacturing over 100 years ago, idecabtagene vicleucel and ciltacabtagene autoleucel have now set the starting point for BCMA CAR-T therapy with their approvals. As with any emerging technology, whether automotive or cellular, the best in innovation and optimization is yet to come.

show abstract

Section: Discussionmentioning

confidence: 99%

Innovation in BCMA CAR-T therapy: Building beyond the Model T

2022

View full text Add to dashboard Cite

show abstract

“…Sharing innate-like and adaptive-like immune functions makes Vγ9Vδ2 T cells very attractive candidates for genetic engineering ( 134 ). Vγ9Vδ2 T cells have successfully been armed with CAR to target the B-cell Maturation Antigen (BCMA) in MM and CD123 in AML ( 135 , 136 ). Interestingly, in vitro data and in vivo mouse models have shown that, unlike conventional anti-CD19 CAR-T cells, ZA-stimulated anti-CD19 Vγ9Vδ2 CAR-T cells from healthy donors can target both CD19 + and CD19 - allogeneic leukemia cells via the non-specific MHC-independent cytotoxic activity elicited by pAgs stimulation ( 137 ).…”

Section: Strategies To Bring Vγ9vδ2 T-cell Immune Interventions To Pr...mentioning

confidence: 99%

Vγ9Vδ2 T-cell immunotherapy in blood cancers: ready for prime time?

2023

View full text Add to dashboard Cite

In the last years, the tumor microenvironment (TME) has emerged as a promising target for therapeutic interventions in cancer. Cancer cells are highly dependent on the TME to growth and evade the immune system. Three major cell subpopulations are facing each other in the TME: cancer cells, immune suppressor cells, and immune effector cells. These interactions are influenced by the tumor stroma which is composed of extracellular matrix, bystander cells, cytokines, and soluble factors. The TME can be very different depending on the tissue where cancer arises as in solid tumors vs blood cancers. Several studies have shown correlations between the clinical outcome and specific patterns of TME immune cell infiltration. In the recent years, a growing body of evidence suggests that unconventional T cells like natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells are key players in the protumor or antitumor TME commitment in solid tumors and blood cancers. In this review, we will focus on γδ T cells, especially Vγ9Vδ2 T cells, to discuss their peculiarities, pros, and cons as potential targets of therapeutic interventions in blood cancers.

show abstract

mRNA‐based chimeric antigen receptor T cell therapy: Basic principles, recent advances and future directions

Xiao,

Lai,

Yuan

et al. 2023

Interdisciplinary Medicine

View full text Add to dashboard Cite

Non‐viral vector chimeric antigen receptor (CAR)‐T cells have garnered increasing attention due to their ability to efficiently eradicate cancer cells while mitigating undesirable side effects. However, the current methods for engineering chimeric antigen receptor T (CAR‐T) cells employ viral vectors that result in permanent CAR expression and potentially severe negative impacts. As a solution to these challenges, triggering transitory expression of CARs in T cells via messenger RNA (mRNA) has emerged as a promising strategy. Currently, electroporation is a common method used to introduce the mRNA encoding the CAR into the T cells. Moreover, there has been increasing attention on the exploration of innovative mRNA delivery systems, including lipid, polymer‐based nanoparticle, exosomes and peptide transduction domains. Additionally, we also explored the functions of different types of mRNA in mRNA‐based CAR‐T cell therapy. The auxiliary mRNA, exemplified by systems such as megaTAL and nuclease transposon systems, demonstrates its capacity to extend CAR‐T cell viability and survival. This perspective offers the current state of mRNA‐based CAR‐T cell therapy and provides valuable insights into future research avenues.

show abstract

Vγ9Vδ2 T cells expressing a BCMA—Specific chimeric antigen receptor inhibit multiple myeloma xenograft growth

Cited by 5 publications

References 35 publications

Innovation in BCMA CAR-T therapy: Building beyond the Model T

Innovation in BCMA CAR-T therapy: Building beyond the Model T

Vγ9Vδ2 T-cell immunotherapy in blood cancers: ready for prime time?

mRNA‐based chimeric antigen receptor T cell therapy: Basic principles, recent advances and future directions

Contact Info

Product

Resources

About