A Correlation Between Differentiation Phenotypes of Infused T Cells and Anti-Cancer Immunotherapy

Ren, Hao; Cao, Kunkun; Wang, Mingjun

doi:10.3389/fimmu.2021.745109

Cited by 14 publications

(11 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clinically, the injection of CD19pbCAR T cells would likely eliminate CD19 + tumor cells in the treatment of patients with B-cell malignancies. Tcm cells show superior persistence and antitumor immunity in T-cell therapy, making them essential for treatment efficacy (18,19). The present study found that the numbers of Tcm cells was greater in preparations of CD19pbCAR-transduced than of CD19lvCAR-infected T cells.…”

Section: Cd19pbcar T Cell Distribution In Mice and Their Specific Targeting Of Subcutaneous Cd19 + Tumorsupporting

confidence: 48%

See 1 more Smart Citation

Evaluation of Nonviral piggyBac and lentiviral Vector in Functions of CD19chimeric Antigen Receptor T Cells and Their Antitumor Activity for CD19+ Tumor Cells

Lin

Liu

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Nonviral transposon piggyBac (PB) and lentiviral (LV) vectors have been used to deliver chimeric antigen receptor (CAR) to T cells. To understand the differences in the effects of PB and LV on CAR T-cell functions, a CAR targeting CD19 was cloned into PB and LV vectors, and the resulting pbCAR and lvCAR were delivered to T cells to generate CD19pbCAR and CD19lvCAR T cells. Both CD19CAR T-cell types were strongly cytotoxic and secreted high IFN-γ levels when incubated with Raji cells. TNF-α increased in CD19pbCAR T cells, whereas IL-10 increased in CD19lvCAR T cells. CD19pbCAR and CD19lvCAR T cells showed similar strong anti-tumor activity in Raji cell-induced mouse models, slightly reducing mouse weight while enhancing mouse survival. High, but not low or moderate, concentrations of CD19pbCAR T cells significantly inhibited Raji cell-induced tumor growth in vivo. These CD19pbCAR T cells were distributed mostly in mesenteric lymph nodes, bone marrow of the femur, spleen, kidneys, and lungs, specifically accumulating at CD19-rich sites and CD19-positive tumors, with CAR copy number being increased on day 7. These results indicate that pbCAR has its specific activities and functions in pbCAR T cells, making it a valuable tool for CAR T-cell immunotherapy.

show abstract

Section: Cd19pbcar T Cell Distribution In Mice and Their Specific Targeting Of Subcutaneous Cd19 + Tumorsupporting

confidence: 48%

“…Tcm cells show superior persistence and antitumor immunity in T-cell therapy, making them essential for treatment efficacy ( 18 , 19 ). The present study found that the numbers of Tcm cells was greater in preparations of CD19pbCAR-transduced than of CD19lvCAR-infected T cells.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Nonviral piggyBac and lentiviral Vector in Functions of CD19chimeric Antigen Receptor T Cells and Their Antitumor Activity for CD19+ Tumor Cells

Lin

Liu

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…The expression of Ki67 allows the identification of proliferating T cells providing a potential means to identify T cell populations that are responding to any immunotherapy or vaccination ( 48 ). CCR7 was included in this panel to assess T cell trafficking, particularly in lymph node samples, and to monitor T cell differentiation ( 49 ).…”

Section: Resultsmentioning

confidence: 99%

Multiparametric flow cytometry to characterize vaccine-induced polyfunctional T cell responses and T cell/NK cell exhaustion and memory phenotypes in mouse immuno-oncology models

et al. 2023

View full text Add to dashboard Cite

Suitable methods to assess in vivo immunogenicity and therapeutic efficacy of cancer vaccines in preclinical cancer models are critical to overcome current limitations of cancer vaccines and enhance the clinical applicability of this promising immunotherapeutic strategy. In particular, availability of methods allowing the characterization of T cell responses to endogenous tumor antigens is required to assess vaccine potency and improve the antigen formulation. Moreover, multiparametric assays to deeply characterize tumor-induced and therapy-induced immune modulation are relevant to design mechanism-based combination immunotherapies. Here we describe a versatile multiparametric flow cytometry method to assess the polyfunctionality of tumor antigen-specific CD4+ and CD8+ T cell responses based on their production of multiple cytokines after short-term ex vivo restimulation with relevant tumor epitopes of the most common mouse strains. We also report the development and application of two 21-color flow cytometry panels allowing a comprehensive characterization of T cell and natural killer cell exhaustion and memory phenotypes in mice with a particular focus on preclinical cancer models.

show abstract

“…It has been reported that CAR-T cells displaying a “less differentiated profile” (namely, central memory cells), persist and, thus, perform better in vivo . 33 Exhausted T cells may become progressively dysfunctional, and this loss of function is mediated by the up-regulation of inhibitory receptors such as programmed death receptor-1 (PD-1), lymphocyte activation gene-3 (LAG-3), T-cell immunoglobulin-3 (TIM-3), and T-cell immunoreceptor with Ig and ITIM domains (TIGIT). 34 We therefore monitored the expression of these exhaustion markers over time in culture.…”

Section: Resultsmentioning

confidence: 99%

Preclinical evaluation and structural optimization of anti-BCMA CAR to target multiple myeloma

et al. 2022

View full text Add to dashboard Cite

Chimeric antigen receptor (CAR) T-cell based immunotherapy has become a promising treatment mainly for hematological malignancies. Following the major success of CD19-targeted CAR, new potential targets for other malignancies are required. As such, BCMA is an attractive tumorassociated antigen to be targeted in multiple myeloma (MM). Herein, we aimed at assessing the function and optimal configuration of different BCMA-specific CARs, based on the same targeting moiety but with a different hinge and co-stimulatory domain. We compared their function to that of a previously characterized BCMA-CAR used in clinical trials. All constructs were expressed at high levels by primary human T-cells and could trigger cytokine production and cytotoxicity upon coculture with multiple myeloma targets. Nonetheless, critical differences were observed in off-target activation, exhaustion, and activation markers expression and in vivo antitumoral activity mediated by these different constructs. Interestingly, we noted that CD8-based hinge, combined with a 4-1BB intracellular domain, proved superior compared to IgG4 connecting regions, and/or a CD28 signaling moiety respectively. Overall, this study emphasizes the influence of CAR primary structure on its function and led to the identification of a highly efficient BCMA-specific CAR, namely H8BB, which displayed superior anti-tumor activity both in vitro and long-term in vivo efficacy.

show abstract

A Correlation Between Differentiation Phenotypes of Infused T Cells and Anti-Cancer Immunotherapy

Cited by 14 publications

References 106 publications

Evaluation of Nonviral piggyBac and lentiviral Vector in Functions of CD19chimeric Antigen Receptor T Cells and Their Antitumor Activity for CD19+ Tumor Cells

Evaluation of Nonviral piggyBac and lentiviral Vector in Functions of CD19chimeric Antigen Receptor T Cells and Their Antitumor Activity for CD19+ Tumor Cells

Multiparametric flow cytometry to characterize vaccine-induced polyfunctional T cell responses and T cell/NK cell exhaustion and memory phenotypes in mouse immuno-oncology models

Preclinical evaluation and structural optimization of anti-BCMA CAR to target multiple myeloma

Contact Info

Product

Resources

About