Lenalidomide enhances CD23.CAR T cell therapy in chronic lymphocytic leukemia

Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME) limit their use of it. Target selection is the most critical aspect in determining the prognosis of patients receiving this treatment. This review provides a comprehensive summary of all therapeutic targets used in the clinic or shown promising potential. We summarize CAR-T cell therapies’ clinical trials, applications, research frontiers, and limitations in treating different cancers. We also explore coping strategies when encountering sub-optimal tumor-associated antigens (TAA) or TAA loss. Moreover, the importance of CAR-T cell therapy in cancer immunotherapy is emphasized.

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“…CAR-T cells targeting Siglec-6 and CD23 separately have been developed, and their effects will be confirmed in future experiments [136,137].…”

Section: Chronic Lymphocytic Leukemia (Cll)mentioning

confidence: 96%

Tumor buster - where will the CAR-T cell therapy ‘missile’ go?

Zhang

Cao

et al. 2022

Mol Cancer

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“…The low-risk group with higher immune scores had smaller IC50 in 15 immunotherapeutic agents (Fig. 7B) [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and was more sensitive to 18 targeted therapeutics (e.g., Nilotinib) and six chemotherapeutic agents (e.g., Vinblastine) than the highrisk group. All 39 chemicals were shown in Fig.…”

Section: Clinical Treatment Response Analysesmentioning

confidence: 99%

Identification and verification of aging-related lncRNAs for prognosis prediction and immune microenvironment in patients with head and neck squamous carcinoma

GAO¹,

SHI²,

Sun³

et al. 2023

Oncology Research

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Aging is highly associated with tumor formation and progression. However, little research has explored the association of aging-related lncRNAs (ARLs) with the prognosis and tumor immune microenvironment (TIME) of head and neck squamous cell carcinoma (HNSCC). RNA sequences and clinicopathological data of HNSCC patients and normal subjects were downloaded from The Cancer Genome Atlas. In the training group, we used Pearson correlation, univariate Cox regression, least absolute shrinkage/selection operator regression analyses, and multivariate Cox regression to build a prognostic model. In the test group, we evaluated the model. Multivariate Cox regression was done to screen out independent prognostic factors, with which we constructed a nomogram. Afterward, we demonstrated the predictive value of the risk scores based on the model and the nomogram using time-dependent receiver operating characteristics. Gene set enrichment analysis, immune correlation analysis, and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic responses. The most important LINC00861 in the model was examined in HNE1, CNE1, and CNE2 nasopharyngeal carcinoma cell lines and transfected into the cell lines CNE1 and CNE2 using the LINC00861-pcDNA3.1 construct plasmid. In addition, CCK-8, Edu, and SA-β-gal staining assays were conducted to test the biofunction of LINC00861 in the CNE1 and CNE2 cells. The signature based on nine ARLs has a good predictive value in survival time, immune infiltration, immune checkpoint expression, and sensitivity to multiple drugs. LINC00861 expression in CNE2 was significantly lower than in the HNE1 and CNE1 cells, and LINC00861 overexpression significantly inhibited the proliferation and increased the senescence of nasopharyngeal carcinoma cell lines. This work built and verified a new prognostic model for HNSCC based on ARLs and mapped the immune landscape in HNSCC. LINC00861 is a protective factor for the development of HNSCC.

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“…CS1 CAR T cells expanded in vitro with lenalidomide had improved anti-tumor efficacy and in vivo persistence in murine myeloma models (47). Preclinical studies showed treatment with lenalidomide during the early phase of in vivo CAR T cell expansion recapitulated the effects of ex vivo lenalidomide exposure in multiple hematologic and solid tumor mouse models (48)(49)(50)(51)(52). As expected, several clinical trials investigating the combination of CAR T cells with lenalidomide have been initiated (NCT03070327, NCT05032820, NCT04923893, NCT04002401).…”

Section: Immune Modulatorsmentioning

confidence: 99%

The magic of small-molecule drugs during ex vivo expansion in adoptive cell therapy

et al. 2023

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In the past decades, advances in the use of adoptive cellular therapy to treat cancer have led to unprecedented responses in patients with relapsed/refractory or late-stage malignancies. However, cellular exhaustion and senescence limit the efficacy of FDA-approved T-cell therapies in patients with hematologic malignancies and the widespread application of this approach in treating patients with solid tumors. Investigators are addressing the current obstacles by focusing on the manufacturing process of effector T cells, including engineering approaches and ex vivo expansion strategies to regulate T-cell differentiation. Here we reviewed the current small-molecule strategies to enhance T-cell expansion, persistence, and functionality during ex vivo manufacturing. We further discussed the synergistic benefits of the dual-targeting approaches and proposed novel vasoactive intestinal peptide receptor antagonists (VIPR-ANT) peptides as emerging candidates to enhance cell-based immunotherapy.

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Lenalidomide enhances CD23.CAR T cell therapy in chronic lymphocytic leukemia

Cited by 16 publications

References 64 publications

Tumor buster - where will the CAR-T cell therapy ‘missile’ go?

Tumor buster - where will the CAR-T cell therapy ‘missile’ go?

Identification and verification of aging-related lncRNAs for prognosis prediction and immune microenvironment in patients with head and neck squamous carcinoma

The magic of small-molecule drugs during ex vivo expansion in adoptive cell therapy

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