Reference Detail

Ref Type

Journal Article

PMID

(33028589)

Authors

Liu H, Lei W, Zhang C, Yang C, Wei J, Guo Q, Guo X, Chen Z, Lu Y, Young KH, Lu Z, Qian W

Title

CD19-specific CAR T Cells that Express a PD-1/CD28 Chimeric Switch-Receptor are Effective in Patients with PD-L1-positive B-Cell Lymphoma.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research	27	2	2021 Jan 15	473-484	Clin Cancer Res

URL

Abstract Text

CD19-specific chimeric antigen receptor (CAR) T-cell therapy is effective against refractory or relapsed (R/R) B-cell lymphoma, but the efficacy is hindered by the existence of PD-1/PD-L1 pathway.Here, we generated a novel anti-CD19 CAR-expressing PD-1/CD28 chimeric switch-receptor (CD19-PD-1/CD28-CAR). We then conducted a phase Ib study to evaluate safety and efficacy of CD19-PD-1/CD28-CAR T cells in the treatment of PD-L1+ B-cell lymphoma.We found that CD19-PD-1/CD28-CAR T cells had superior T-cell proliferation, cytokine production, and sequentially capability of killing PD-L1+ B-cell lymphoma cells in vitro and in vivo relative to the prototype, CD19-CAR T cells. Among 17 adult patients with R/R lymphoma who received the CAR T therapy, 10 patients had objective response (58.8%), including seven patients with complete remission (41.2%). At a median follow-up 15 months, median overall survival for all patients was not reached. Remarkably, no severe neurologic toxicity or cytokine release syndrome was observed.This first-in-human study demonstrates the tolerability, safety, and encouraging efficacy of CD19-PD-1/CD28-CART in PD-L1+ large B-cell lymphoma.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
CD19-PD-1/CD28-CAR T cells	CD19-PD-1/CD28-CAR T cells	2	0

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
CD19-PD-1/CD28-CAR T cells				CD19-PD-1/CD28-CAR T cells consist of autologous T-lymphomcytes engineered to produce a chimeric antigen receptor (CAR) with an anti-CD19 fragment and a PD-1/CD28 chimeric switch-receptor, which may lead to potential cytotoxic activity against tumor cells expressing PD-L1 (PMID: 33028589).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CD274 over exp	B-cell lymphoma	sensitive	CD19-PD-1/CD28-CAR T cells	Preclinical - Cell line xenograft	Actionable	In a preclinical study, CD19-PD-1/CD28 CAR T cell treatment induced dose-dependent cytotoxicity against a B cell lymphoma cell line with CD274 overexpression in culture, and resulted in greater inhibition of tumor growth in a cell line xenograft model compared to treatment with anti-CD19 CAR T cells alone or combined with an anti-PD-1 antibody (PMID: 33028589).	33028589
CD274 positive	diffuse large B-cell lymphoma	predicted - sensitive	CD19-PD-1/CD28-CAR T cells	Case Reports/Case Series	Actionable	In a Phase Ib trial, CD19-PD-1/CD28-CAR T cell treatment in two patients with CD274 positive diffuse large B-cell lymphoma resulted in complete remission (CR) after 3 months, however, disease progression was observed in one patient after 2 months, while the other patient achieved persistent CR. (PMID: 33028589).	33028589