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Fc-optimized CD40 Agonistic Antibody Induces Tertiary Lymphoid Structures and Systemic Antitumor Immunity in Metastatic Cancer Patients [Human]

ABSTRACT: Fc-optimized CD40 Agonistic Antibody Induces Tertiary Lymphoid Structures and Systemic Antitumor Immunity in Metastatic Cancer Patients [Human]

PROVIDER: PRJNA1267166 | ENA |

REPOSITORIES: ENA

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Fc-optimized CD40 Agonistic Antibody Induces Tertiary Lymphoid Structures and Systemic Antitumor Immunity in Metastatic Cancer Patients

Project description:Fc-optimized CD40 Agonistic Antibody Induces Tertiary Lymphoid Structures and Systemic Antitumor Immunity in Metastatic Cancer Patients

| PRJNA1267139 | ENA

Transcriptomic analysis of 4NQO-induced oral squamous cell carcinoma with agonistic anti-CD40 treatment

Project description:To investigate the anti-tumor effect of agonistic anti-CD40, 4NQO-indued OSCC mice with agonistic anti-CD40.

2023-10-23 | GSE217407 | GEO

Fc-optimized CD40 Agonistic Antibody Induces Tertiary Lymphoid Structures and Systemic Antitumor Immunity in Metastatic Cancer Patients

Project description:These studies were performed to understand the transcriptional profile of immune cells following treatment with 2141-V11, the main comparison was injected tumors versus non-injected ones. In summary: hCD40/hFcγR mice were inoculated bilaterally with E0771 tumors (5*105). IT 2141-V11 or isotype-matched control Abs were given into one tumor (the largest of the two) on days 14 and 17. Both tumors were excised on day 18 for scRNAseq and TCR-seq of CD45+ cells.

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Fc-optimized CD40 Agonistic Antibody Induces Tertiary Lymphoid Structures and Systemic Antitumor Immunity in Metastatic Cancer Patients [Human]

Project description:Human peripheral blood mononuclear cells (PBMC) from participants of the clinical study were isolated and thawed using prewarmed BD BSA stain buffer (BD Biosciences), washed twice with ice-cold buffer and counted and CD45+ cells were sorted for RNA sequencing.

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IL-15 complex enhances agonistic anti-CD40 + anti-PDL1 by correcting the T-bet to Tox ratio in CD8+ T cells infiltrating pancreatic ductal adenocarcinoma

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Bispecific antibodies increase the therapeutic window of CD40 agonists through selective dendritic cell targeting

Project description:Therapeutic use of agonistic anti-CD40 antibodies is a potentially powerful approach for activating the immune response to eradicate tumors. However, the translation of this approach to clinical practice has been significantly restricted due to the severe dose-limiting toxicities observed in multiple clinical trials. Here, we demonstrate that conventional type-1 dendritic cells are essential for triggering antitumor immunity but not toxicity by CD40 agonists, while macrophages, platelets, and monocytes lead to the toxic events. Therefore, we designed bispecific antibodies that target CD40 activation preferentially to dendritic cells. These bispecific reagents demonstrate a superior safety profile compared to their parental CD40 monospecific antibody, while triggering potent anti-tumor activity. We suggest such cell-selective bispecific agonistic antibodies as a drug platform to bypass the dose-limiting toxicities of anti-CD40, and of additional types of agonistic antibodies used for cancer immunotherapy.

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Cd40

Project description:Rattus norvegicus Cd40, CD40 molecule [Source:RGD Symbol;Acc:619830], is expressed in 4 baseline experiment(s);

| ENSRNOG00000018488 | ExpressionAtlas

Cd40

Project description:Rattus norvegicus Cd40, CD40 molecule [Source:RGD Symbol;Acc:619830], is differentially expressed in 22 experiment(s);

| ENSRNOG00000018488 | ExpressionAtlas

Combinatorial immunotherapy with agonistic CD40 activates dendritic cells to express IL-12 and overcome PD-1 resistance

Project description:Combinatorial immunotherapy with agonistic CD40 activates dendritic cells to express IL-12 and overcome PD-1 resistance