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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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			Action	DRS
	SRR33686600_1.fastq.gz	Fastqsanger.gz
	SRR33686600_2.fastq.gz	Fastqsanger.gz
	SRR33686601_1.fastq.gz	Fastqsanger.gz
	SRR33686601_2.fastq.gz	Fastqsanger.gz
	SRR33686602_1.fastq.gz	Fastqsanger.gz

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

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

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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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