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Series GSE184009 Query DataSets for GSE184009
Status Public on Dec 12, 2021
Title Bispecific antibodies increase the therapeutic window of CD40 agonists through selective dendritic cell targeting
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
 
Overall design 2 MARS seq experiments were done: 1) MC38 tumor bearing mice were treated with either mono specific CD40 (5 mice), bi specific CD40/CD11c (7 mice) and PBS (6 mice), and harvested 7 days post treatment for single-cell RNA seq analysis. 2) Mice were treated with mono specific CD40 (2 mice) and bi specific CD40/CD11c 92 mice). 3 hours post treatment LN and spleen were harvested and pooled together from each 2 mice for single-cell RNA seq analysis.
 
Contributor(s) Salomon R, Rotem H, Katzenelenbogen Y, Weiner A, Saban NC, Feferman T, Amit I, Dahan R
Citation(s) 35190724
Submission date Sep 13, 2021
Last update date Mar 13, 2022
Contact name Ido Amit
E-mail(s) ido.amit@weizmann.ac.il
Phone 972-8-9343338
Organization name Weizmann Institute of Science
Department Immunology
Street address 234 Herzl st.
City Rehovot
ZIP/Postal code 760001
Country Israel
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (160)
GSM5575686 AB10837
GSM5575687 AB10838
GSM5575688 AB10839
Relations
BioProject PRJNA762698
SRA SRP336805

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE184009_final_mat.csv.gz 39.0 Mb (ftp)(http) CSV
GSE184009_metadata.txt.gz 599.0 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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