CS1003, a novel human and mouse cross-reactive PD-1 monoclonal antibody for cancer therapy

Fu, Li; Li, Jingrong; Yin, Ke; Zhang, Juan; Li, Zhenhu; Lu, Liang; Bao, Yuanwu; Qin, Zhen; Zheng, Yong; Yang, Baotian; Li, Jing; Wang, Xinzhong

doi:10.1038/s41401-020-0422-6

Cited by 10 publications

(10 citation statements)

References 18 publications

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“…5B). These results are consistent with previous observations including our own showing that subcutaneous MC38 tumors respond well to anti-PD1 therapy in both early-and latetreatment paradigms, whereas subcutaneous KPC tumors do not (23)(24)(25)(26). In particular, our analysis of the PD1-PDL1 axis by simultaneously profiling both the non-immune and immune compartments further supports the previously established role of PDL1 expression in both the tumor cells and TAMs in the immune escape of MC38 tumors (25,(27)(28)(29).…”

Section: Live Cell Barcoding System Allows Multiplexed Mouse Tumor Prsupporting

confidence: 93%

“…Furthermore, when we compared the expression levels of PDL1 at the per-cell level within each cell type cluster (i.e., cell states instead of cell type abundances), the top 2 CD45 – cell clusters, annotated as Tumor 1 and Tumor 2, showed substantial and statistically significant differences in PDL1 expression, again showing that MC38 tumors have higher PDL1 expression within the CD45 – compartment ( Figure 5B ). These results are consistent with previous observations including our own showing that s.c. MC38 tumors respond well to anti-PD1 therapy in both early- and late-treatment paradigms, whereas s.c. KPC tumors do not ( 23 – 26 ). In particular, our analysis of the PD1-PDL1 axis by simultaneously profiling both the nonimmune and immune compartments further supports the previously established role of PDL1 expression in both the tumor cells and TAMs in the immune escape of MC38 tumors ( 25 , 27 – 29 ).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

A global live cell barcoding approach for multiplexed mass cytometry profiling of mouse tumors

Charmsaz

Groß

Jaffee³

et al. 2021

JCI Insight

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Conflicts of interest: W.H. reports co-inventorship of patents with potential for receiving royalties from Rodeo Therapeutics, receiving research grant from Sanofi, and consulting for Exelixis. E.M.J. reports receiving a commercial research grant from Bristol-Myers Squibb, Aduro Biotech, and Amgen, has ownership interest (including stock, patents, etc.) in Aduro Biotech, and is a consultant/advisory board member for CStone, Dragonfly, Genocea, and Adaptive Biotechnologies.

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Section: Live Cell Barcoding System Allows Multiplexed Mouse Tumor Prsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

A global live cell barcoding approach for multiplexed mass cytometry profiling of mouse tumors

Charmsaz

Groß

Jaffee³

et al. 2021

JCI Insight

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“…The interaction between PD-1 and PD-L1 inhibits T cell activation . Therefore, we investigated the effects of AFT/2-BP@PLGA@MD on T cells in a coculture model.…”

Section: Resultsmentioning

confidence: 99%

“…The interaction between PD-1 and PD-L1 inhibits T cell activation. 33 Therefore, we investigated the effects of AFT/2-BP@PLGA@MD on T cells in a coculture model. We found that coculture of CHO-K1-hPD-L1 cells inhibited the activation and proliferation of Jurkat cells.…”

Section: Resultsmentioning

confidence: 99%

Intelligent Biomimetic Nanoplatform for Systemic Treatment of Metastatic Triple-Negative Breast Cancer via Enhanced EGFR-Targeted Therapy and Immunotherapy

Wang

Zhu

et al. 2022

ACS Appl. Mater. Interfaces

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Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer, and it is associated with a high recurrence rate, metastatic potential, and poor prognosis. Thus, effective therapeutic strategies for TNBC are urgently required. The epidermal growth factor receptor (EGFR) is considered to be a potential therapeutic target for TNBC. However, there are limitations to the use of targeted therapies, such as afatinib (AFT), particularly drug resistance. Here, we investigated a poly(d,l-lactide-glycolide) (PLGA)-based intelligent bionic nanoplatform, termed AFT/2-BP@PLGA@MD, which combined targeted therapy with immunotherapy. In this platform, PLGA was used to encapsulate 2-bromo-palmitate (2-BP), a palmitoylation inhibitor, to enhance the efficacy of AFT against TNBC cells. PLGA was coated with a cancer cell membrane anchored with a cleavable peptide by matrix metalloproteinase-2 to block programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1). 2-BP significantly enhanced the capacity of AFT to inhibit the proliferation and migration of tumor cells in vitro. Moreover, the tumor cell membrane-coated AFT/2-BP@PLGA@MD nanoparticles exhibited enhanced tumor targeting ability in vivo. The AFT/2-BP@PLGA@MD nanoparticles significantly inhibited the growth and metastasis of 4T1 tumor and prolonged the survival of tumor-bearing mice. The nanoparticles also triggered antitumor immune response. Collectively, we report an effective therapeutic strategy for clinically refractory TNBC.

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“…The HTLV-1–derived gene pol was negative ( 8 ), excluding adult T cell leukemia/lymphoma (ATLL) ( Supplemental Figure 1 ; supplemental material available online with this article; https://doi.org/10.1172/jci.insight.164793DS1 ). The patient was diagnosed as advanced MF (stage IVA1) and was enrolled in a phase IA clinical trial of a humanized IgG4 anti–PD-1 monoclonal antibody ( 9 ) in advanced lymphomas and solid tumors (NCT03809767). He was given an initial dose of 60 mg monotherapy, in a plan for dose escalation.…”

Section: Resultsmentioning

confidence: 99%

Hyperprogression of cutaneous T cell lymphoma after anti–PD-1 treatment

Gao¹,

Hu²,

Li³

et al. 2023

JCI Insight

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BACKGROUND. Immune checkpoint blockade is an emerging treatment for T cell non-Hodgkin lymphoma (T-NHL), but some T-NHL patients have experienced hyperprogression with undetermined mechanisms upon anti-PD-1 therapy.METHODS. Single-cell RNA sequencing, whole-genome sequencing, whole-exome sequencing, and functional assays were performed on primary malignant T cells from a patient with advanced cutaneous T cell lymphoma, who experienced hyperprogression upon anti-PD-1 treatment.RESULTS. The patient was enrolled in a clinical trial of anti-PD-1 therapy and experienced disease hyperprogression. Single-cell RNA sequencing revealed that PD-1 blockade elicited a remarkable activation and proliferation of the CD4+ malignant T cells, which showed functional PD-1 expression and an exhausted status. Further analyses identified somatic amplification of PRKCQ in the malignant T cells. PRKCQ encodes PKCθ, a key player in the T cell activation/NF-kB pathway. PRKCQ amplification led to high expressions of PKCθ and p-PKCθ (T538) on the malignant T cells, resulting in an oncogenic activation of the T cell receptor (TCR) signaling pathway. PD-1 blockade in this patient released this signaling, de-repressed the proliferation of malignant T cells, and resulted in disease hyperprogression. 30CONCLUSIONS. Our study provides real-world clinical evidence that PD-1 acts as a tumor suppressor for malignant T cells with oncogenic TCR activation. TRIAL REGISTRATION. ClinicalTrials.gov (NCT03809767).

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CS1003, a novel human and mouse cross-reactive PD-1 monoclonal antibody for cancer therapy

Cited by 10 publications

References 18 publications

A global live cell barcoding approach for multiplexed mass cytometry profiling of mouse tumors

A global live cell barcoding approach for multiplexed mass cytometry profiling of mouse tumors

Intelligent Biomimetic Nanoplatform for Systemic Treatment of Metastatic Triple-Negative Breast Cancer via Enhanced EGFR-Targeted Therapy and Immunotherapy

Hyperprogression of cutaneous T cell lymphoma after anti–PD-1 treatment

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